Dose enhancement effect of anticaner drugs associated with increased temperature in vitro

Dose enhancement effect of anticaner drugs associated with increased temperature in vitro

Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min...

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Datum:2008
Hauptverfasser: Istomin, Yu.P., Zhavrid, E.A., Alexandrova, E.N., Sergeyeva, O.P., Petrovich, S.V.
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Veröffentlicht: Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України 2008
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spelling irk-123456789-1392272018-06-21T03:05:46Z Dose enhancement effect of anticaner drugs associated with increased temperature in vitro Istomin, Yu.P. Zhavrid, E.A. Alexandrova, E.N. Sergeyeva, O.P. Petrovich, S.V. Uncategorized Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 °C or 42 °C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. Results: Hyperthermia alone caused only 10–20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. Conclusion: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect. Цель: изучить in vitro влияние повышенной температуры (42 °C в течение 60 мин) на действие противоопухолевых препаратов: доксорубицина, винорельбина, карбоплатина, ифосфамида, этопозида, оксалиплатина, доцетаксела и гемцитабина. Методы: культуру опухолевых клеток HeLa через 24 ч после рассева инкубировали в течение 60 мин с различными концентрациями химиотерапевтических препаратов при температуре 37 °C или 42 °C. Спустя 48 ч подсчитывали количество живых клеток во флаконах, используя гемоцитометр и метод исключения красителя трипанового синего. Результаты: гипертермия сама по себе вызывала 10–20% угнетение роста культуры клеток. У всех исследованных химиотерапевтических препаратов отмечали эффект усиления при повышенной температуре. Коэффициент теплового усиления в отношении клеточной пролиферации для оксалиплатина, винорельбина, карбоплатина и ифосфамида превысил 4,0, для доксорубицина и гемцитабина — 2,0. Коэффициент теплового усиления в отношении гибели клеток не превышал 1,4. Выводы: синергизм гипертермии и химиотерапевтических препаратов продемонстрирован для оксалиплатина, винорельбина, карбоплатина, ифосфамида, в меньшей степени — для доксорубицина и гемцитабина. Усиление цитостатического эффекта противоопухолевых препаратов под действием гипертермии было более выраженным, чем их цитотоксического эффекта. 2008 Article Dose enhancement effect of anticaner drugs associated with increased temperature in vitro / Yu.Р. Istomin, E.A. Zhavrid, E.N. Alexandrova, O.P. Sergeyeva, S.V. Petrovich // Experimental Oncology. — 2008. — Т. 30, № 1. — С. 56–59. — Бібліогр.: 28 назв. — англ. 1812-9269 http://dspace.nbuv.gov.ua/handle/123456789/139227 en Experimental Oncology Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
institution Digital Library of Periodicals of National Academy of Sciences of Ukraine
collection DSpace DC
language English
topic Uncategorized
Uncategorized
spellingShingle Uncategorized
Uncategorized
Istomin, Yu.P.
Zhavrid, E.A.
Alexandrova, E.N.
Sergeyeva, O.P.
Petrovich, S.V.
Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
Experimental Oncology
description Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 °C or 42 °C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. Results: Hyperthermia alone caused only 10–20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. Conclusion: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect.
format Article
author Istomin, Yu.P.
Zhavrid, E.A.
Alexandrova, E.N.
Sergeyeva, O.P.
Petrovich, S.V.
author_facet Istomin, Yu.P.
Zhavrid, E.A.
Alexandrova, E.N.
Sergeyeva, O.P.
Petrovich, S.V.
author_sort Istomin, Yu.P.
title Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
title_short Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
title_full Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
title_fullStr Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
title_full_unstemmed Dose enhancement effect of anticaner drugs associated with increased temperature in vitro
title_sort dose enhancement effect of anticaner drugs associated with increased temperature in vitro
publisher Інститут експериментальної патології, онкології і радіобіології ім. Р.Є. Кавецького НАН України
publishDate 2008
topic_facet Uncategorized
url http://dspace.nbuv.gov.ua/handle/123456789/139227
citation_txt Dose enhancement effect of anticaner drugs associated with increased temperature in vitro / Yu.Р. Istomin, E.A. Zhavrid, E.N. Alexandrova, O.P. Sergeyeva, S.V. Petrovich // Experimental Oncology. — 2008. — Т. 30, № 1. — С. 56–59. — Бібліогр.: 28 назв. — англ.
series Experimental Oncology
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fulltext 56 Experimental Oncology 30, 56–59, 2008 (March) Multiple studies in hyperthermic oncology testify the enhancing efficacy of combination or multimodali­ ty therapy of cancer patients by application of high temperature (40–43 °C for whole­body exposure and 42–47 °C for local treatment). Hyperthermia has been shown to be a powerful modifying factor that increases tumor sensitivity to both radio­ and chemotherapy [1–6]. Thermal enhancement of cytotoxic effects for many anticancer drugs has been observed in diffe rent experimental systems. The mechanisms involved in the interaction of chemotherapy and hyperthermia are depended on the particular chemotherapeutic agent and thought to be related to an increase in drug uptake, expand of DNA damage and inhibition of DNA repair [1–3, 7]. In vitro drug­induced cell killing usu­ ally increased with temperature from 40 °C to 45 °C and maximal cytotoxicity occurred when the drug was scheduled simultaneously with hyperthermia. In vivo the therapeutic efficacy of the thermotherapy was maximized at mild temperature (40.5–43 °C) and the greatest potentiation occurred when the two modali­ ties were administered close together [2, 6, 7]. Despite several experimental studies on the inter­ action of hyperthermia with chemotherapeutic drugs data concerning treatment efficiency are often con­ flicting. The use of various cell lines, different treatment schemes and differing end points complicates the interpretation of research findings. Drug concentration and drug exposure time are also of great importance. Furthermore, in vitro and vivo results often differ due to physiology factors of tumor tissue such as micro­ circulation, pH and oxygenation. Alkylating agents melphalan, cyclophosphamide and ifosfamide were shown to be the most effective drug at moderately elevated temperatures for many types of tumors, effectiveness of cisplatin or oxali­ platin was less pronounced [8, 9, 10]. Hyperthermia was proved to enhance the sensitivity of human tumor cells to doxorubicin [7, 11, 12], vincristine [12] and carboplatin [13, 14], whereas the efficacy of etoposide is only slightly influenced by additional application of heat [15, 16] or decreased [17]. However it was demonstrated that appropriately scheduled hyper­ thermia and etoposide treatments result in increased etoposide­induced death of human leukemia cells [18]. Simultaneous application of gemcitabine and heat led to decreased cytotoxicity [19, 20], had not the influence on cytotoxicity [12] or augmented cytotoxic effect of drug [10, 21, 22]. There are also contradictory reports as to the interaction of hyperthermia and the taxanes [10, 23–28]. Therefore it is important to compare in equal treat­ ment conditions the impact of hyperthermia on the action of the main chemotherapeutic drugs currently used for cancer treatment. In this study we investigated the differences in HeLa tumor cell culture growth after incubation with different anticancer drugs at a tem­ perature of 37 °C or 42 °C. MATERIALS AND METHODS Chemotherapeutic drugs. The drugs investiga­ ted were ifosfamide (holoxan, Baxter Oncology Gmbx, Germany), doxorubicin (doxorubicin hydrochloride, RUE “Belmedpreparaty”, Belarus), carboplatin (carboplatin­LENS, Veropharm, Russia), oxaliplatin (eloxatin, Sanofi­Synthelabo, France), vinorelbin (neocitec, Labinca, Argentina), etoposide (etoposide­ LENS, Veropharm, Russia), docetaxel (docetal, Dabur Pharma Ltd., India), gemcitabine (gemzar, “Eli Lilly”, USA). Just before use, the drugs were diluted with culture medium. DOSE ENHANCEMENT EFFECT OF ANTICANER DRUGS ASSOCIATED WITH INCREASED TEMPERATURE IN VITRO Yu.Р. Istomin*, E.A. Zhavrid, E.N. Alexandrova, O.P. Sergeyeva, S.V. Petrovich N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk 223040, Belarus Aim: To evaluate in vitro the influence of elevated temperature (42 °C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine. Methods: HeLa tumor cell cultures, 24 h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 °C or 42 °C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer. Results: Hyperthermia alone caused only 10–20% growth inhibition of cell culture. All the chemotherapeutic drugs used demonstrated a dose enhancement effect at elevated temperature. Thermal enhancement ratio for cell proliferation for oxaliplatin, vinorelbine, carboplatin and ifosfamide exceeded 4, for doxorubicin and gemcitabine exceeded 2. Thermal enhancement ratio for cell death did not exceed 1.4. Conclusion: Synergism of hyperthermia and chemotherapeutical drugs was clearly demonstrated for oxaliplatin, vinorelbine, carboplatin, ifosfamide and to a lesser extent for doxorubicin and gemcitabine. Enhancement of the cytostatic effect of anticancer drugs by hyperthermia was more prominent than their cytotoxic effect. Key words: hyperthermia, anticancer drugs, HeLa cells, thermal enhancement ratio. Received: January 16, 2008. *Correspondence: E-mail: istomin06@mail.ru Abbreviations used: IC50 (IC90) — the drug concentration causing a 50% (90%) growth inhibition; LC50 – the drug concentration causing a 50% cell killing; TER – thermal enhancement ratio. Exp Oncol 2008 30, 1, 56–59 Experimental Oncology 30, 56–59, 2008 (March) 5730, 56–59, 2008 (March) 57March) 57) 57 57 Cell culture. HeLa cells (human cervical carci­ noma) were obtained from the cell culture collection of Research Institute of Epidemiology and Microbiology (RIEM, Minsk, Belarus). The cells were cultured as a monolayer in culture flasks covered with 199 medium (RIEM) supplemented with 10% fetal calf serum (RIEM) and 100 µg/ml kanamycin. Cell treatment. One day before the drug treat­ ment, cell monolayer was detached from the culture flasks with 0.02% versen (DIALEK, Belarus) and plated at a concentration of 2 × 105 cells/flask. All the experiments were carried out on exponentially growing cells. On the day of the experiment, 100 µl of each drug dilutions were added into the flasks with cell monolayer and then the cells were incubated in water bath at 37.0 °C ± 0.1 °C or 42.0 °C ± 0.1 °C for 60 min. Treated and control cells were cultured for additional 48 h, then cell monolayers were versenized and viable cells were counted using trypan­blue exclusion on a haemocytometer. The mean ± standard deviation was calculated from three experiments. To differentiate between cytostatic and cytotoxic effects, the number of viable cells after the treatment was compared with the initial cell number before any treatment. Percentage of viable cells above the initial cell number denoted a cytostatic effect, whereas those below showed cytotoxicity [23]. The percentages of viable cells for each treatment were calculated from 100 × [(Nt–No) / (Nk–No)], if Nt was greater than or equal No, or 100 × [(Nt–No) / No], if Nt was less than No (Nt — cell number in treated cultures with chemothera­ peutic drug and/or hyperthermia; Nk — cell number in control cultures that had not been exposed to chemo­ therapeutic drugs or hyperthermia; No — initial cell number before the treatment). The values of IC50 and IC90, concentrations of each drug required for a 50% and 90% reduction in cell number relative to control value, and LC50, concen­concen­ tration of drug required for a 50% reduction in cell number relative to initial value before the treatment, were determined for each experiment using regression analysis of the data received. Thermal enhancement ratios for inhibition of cell proliferation and cell killing for each chemotherapeutic drug were calculated as IC50, IC90, or LC50 for drug alone divided by IC50, IC90, or LC50 for drug combined with hyperthermia. RESULTS AND DISCUSSION The survivals of exponentially growing HeLa cells exposed to various concentration of ifosfamide doxo­ rubicin, carboplatin, docetaxel, vinorelbine, etoposide, oxaliplatin or gemcitabine at 37 °C or 42 °C are shown in Figure. These data demonstrate that cell number reduced with increasing concentrations of chemother­ apeutic agents. All used drugs demonstrated the dose­ dependent enhancement of cytotoxicity at elevated temperature — the decrease of cell number at 42 °C was more pronounced than at 37 °C. It must be noted the heat treatment alone did not alter significantly cell number causing only 10–20% growth inhibition. 0.0 0.5 1.0 1.5 2.0 2.5 50 100 150 200 250 300 350 400 450 500 Ifosfamide, 37 °C Ifosfamide, 42 °C Ce ll nu m be r (1 03 ) Ifosfamide concentration, mg/ml Ce ll nu m be r (1 03 ) 0 200 400 600 800 1000 100 200 300 400 500 600 Doxorubicin, 37 °C Doxorubicin, 42 °C Doxorubicin concentration, ng/ml 0 2 4 6 8 10 0 100 200 300 400 500 Vinorelbin, 37 °C Vinorelbin, 42 °C Vinorelbin concentration, ng/ml Ce ll nu m be r (1 03 ) 0 2 4 6 8 10 100 200 300 400 500 600 700 Etoposide, 37 °C Etoposide, 42 °C Etoposide concentration, µg/ml Ce ll nu m be r (1 03 ) 0 5 10 15 20 0 100 200 300 400 500 600 700 Oxaliplatin, 37 °C Oxaliplatin, 42 °C Oxaliplatin concentration, µg/ml Ce ll nu m be r (1 03 ) 0 100 200 300 400 200 300 400 500 600 700 800 Gemcitabine, 37 °C Gemcitabine, 42 °C Gemcitabine concentration, µg/ml Ce ll nu m be r (1 03 ) 0 10 20 30 40 50 0 100 200 300 400 500 600 700 800 900 Docetaxel, 37 °C Docetaxel, 42 °C Docetaxel concentration, ng/ml Ce ll nu m be r (1 03 ) 0 10 20 30 40 50 0 100 200 300 400 500 600 700 800 Carboplatin, 37 °C Carboplatin, 42 °C Carboplatin concentration, (µg/ml) Ce ll nu m be r (1 03 ) Figure. Dose­response curves for HeLa cells treated with ifosfa­ mide, doxorubicin, carboplatin, oxaliplatin, vinorelbine, etoposide, docetaxel or gemcitabine at 37 °С or 42 °С. The cells were incubated with different concentration of anticancer drug for 1 h at 37 °C or 42 °C and counted 48 h later. Each data point represents the mean of three separate experiments. Bars are standard errors The parameters of cytostatic (IC50 and IC90) and cytotoxic (LC50) effects of chemotherapeutic drugs at 37 °C and 42 °C are presented in Table. The data obtained testify the enhanced efficiency at elevated temperature to a greater or lesser extent of all the drugs under investigation. So, by IC50 and IC90 crite­crite­ ria, hyperthermia caused significant enhancement of cell culture growth inhibition induced by ifosfamide, carboplatin, vinorelbine, oxaliplatin, with thermal en­ hancement ratio exceeded 4. The values of IC50 and IC90 decreased actually for vinorelbine 5.5­fold and for oxaliplatin 7.2­fold after combination with heat. To a lesser degree hyperthermia enhanced cytostatic effect of doxorubicin and gemcitabine, with thermal enhancement ratio exceeded 2. The differences in IC50 and IC90 for docetaxel and etoposide were not significant statistically. By LC50 criterion, statistically 58 Experimental Oncology 30, 56–59, 2008 (March) significant enhancement of drug­mediated cytotoxici­ ty under elevated temperature was observed only for carboplatin, vinorelbine, docetaxel and oxaliplatin, with thermal enhancement ratio for cell death did not exceed 1.4. Thus, thermal enhancement for drug­ mediated inhibition of cell proliferation by combination of chemotherapeutic drugs with hyperthermia was more pronounced than for drug­mediated cell killing. The most efficient chemotherapeutic drugs in HeLa cells at elevated temperature 42 °C were ifosfamide, carboplatin, vinorelbine and oxaliplatin. In this study we investigated in cell culture the action of eight anticancer drugs in broad range of concentrations to describe their both cytostatic and cytotoxic effects. To quantitatively evaluate the impact of the hyperthermia on the chemosensitivity of tumor cells we compared the values of IC50, IC90, and LC50 for dose­response curves of HeLa cell culture treated with chemotherapeutic drugs alone or in combination with heat. It was found that interaction of hyperther­ mia and simultaneous chemotherapy depends on the drug concentration. At low doses of chemothera­ peutic agents that exerted mainly cytostatic effect it was shown synergistic interaction with heat for all the drugs under investigation except for docetaxel and etoposide, whereas at high doses of drugs that exerted predominantly cytotoxic action their interaction with heat was only additive. Thermal enhancement of the cytostatic effect we have observed in this study in vitro may be of impor­ tance under in vivo conditions where events inducing the delay of tumor growth are expected to be cytostatic rather than cytotoxic [10]. We believe the data present in this study have clinical implication having recently begun animal tumor experiments to evaluate efficiency of the same chemotherapy in protocols with whole­ body hyperthermia. REFERENCES 1. Zhavrid EA, Osinsky SP, Fradkin SZ. Hyperthermia and hyperglicemia in oncology. Kiev: Naukova dumka, 1987. 256 p (In Russian). 2. Urano M, Kuroda M, Nishimura Y. For the clinical ap- plication of thermochemotherapy given at mild temperatures. Int J Hyperthermia 1999, 15: 79–107. 3. Falk MH, Issels RD. Hyperthermia in oncology. Int J Hyperthermia 2001, l7: 1–18. 4. Fradkin SZ, Zhavrid EA, Istomin YuP. Promising trends in the development of systemic hyperthermia in multimodality therapy for malignant neoplasms. In: Book of Abstracts 23-d Annual Meeting of the European Society for Hyperthermic Oncology. Berlin, 2006: 22–4. 5. Shevchenko AI, Ganul VL, Ganul AV, Osinsky DS. Hy- perthermia in oncology: achievements and original methods. Oncology 2006, 8: 222–7 (In Ukrainian). 6. Sugarbaker PH. Laboratory and clinical basis for hyper- thermia as a component of intracavitary chemotherapy. Int J Hyperthermia 2007, 23: 431–42. 7. Hahn GM. Potential for therapy of drugs and hyperther- mia. Cancer Res 1979, 39: 2264–8. 8. Urano M, Ling CC. Thermal enhancement of melphalan and oxaliplatin cytotoxicity in vitro. Int J Hyperthermia 2002, 18: 307–15. 9. 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The values of IC50, IC90, and LC50 of dose-response curves for HeLa cells treated with different chemotherapeutic drugs at a temperature of 37 °С or 42 °С Drug IC50 IC90 LC50 37 °С 42 °С TER 37 °С 42 °С ER 37 °С 42 °С TER Ifosfamide (mg/ml) 1.7 ± 0.1 0.4 ± 0.1* 4.3 > 2.5 1.1 ± 0.1* > 2.3 > 2.5 2.3 ± 0.1 > 1.1 Doxorubicin (ng/ml) 8.1 ± 1.8 8.1 ± 1.6 1 106.2 ± 1.8 37.7 ± 1.6* 2.8 > 1000 > 1000 – Carboplatin (µg/ml) 11.7 ± 1.7 2.7 ± 1.9* 4.3 32.1 ± 1.7 14.1 ± 1.9* 2.3 48.9 ± 1.7 36.8 ± 1.9* 1.3 Vinorelbine (ng/ml) 1.1 ± 0.3 0.2 ± 0.3* 5.5 2.5 ± 0.3 0.6 ± 0.3* 4.2 7.4 ± 0.3 6.0 ± 0.3* 1.2 Docetaxel (ng/ml) 5.6 ± 1.9 4.2 ± 2.3 1.3 18.0 ± 1.9 13.9 ± 2.3 1.3 35.2 ± 1.9 24.6 ± 2.3* 1.4 Etoposide (µg/ml) 0.1 ± 0.1 0.1 ± 0.1 1.0 0.7 ± 0.1 0.5 ± 0.1 1.4 > 10 9.2 ± 0.1 > 1.1 Oxaliplatin (µg/ml) 0.4 ± 0.6 0.2 ± 0.2 2.0 3.6 ± 0.6 0.5 ± 0.2* 7.2 8.6 ± 0.6 6.5 ± 0.2* 1.3 Gemcitabine (µg/ml) 26.8 ± 20.2 25.3 ± 12.8 1.1 187.7 ± 20.2 84.4 ± 12.8* 2.2 > 400 > 400 – TER – thermal enhancement ratio calculated as IC50, IC90, or LC50 for drug alone divided by IC50, IC90, or LC50 for drug combined with hyperthermia. *The difference between the values for 37 °С and 42 °С are statistically significant, with р < 0,01. 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Docetaxel and hyperthermia: factors that modify thermal enhancement. J Surg Oncol 2004, 88: 14–20. ЭФФЕКТ УСИЛЕНИЯ АКТИВНОСТИ ПРОТИВООПУХОЛЕВЫХ ПРЕПАРАТОВ ПРИ ПОВЫШЕНИИ ТЕМПЕРАТУРЫ IN VITRO Цель: изучить in vitro влияние повышенной температуры (42 °C в течение 60 мин) на действие противоопухолевых препаратов: доксорубицина, винорельбина, карбоплатина, ифосфамида, этопозида, оксалиплатина, доцетаксела и гемцитабина. Методы: культуру опухолевых клеток HeLa через 24 ч после рассева инкубировали в течение 60 мин с различными концентрациями химиотерапевтических препаратов при температуре 37 °C или 42 °C. Спустя 48 ч подсчитывали количество живых клеток во флаконах, используя гемоцитометр и метод исключения красителя трипанового синего. Результаты: гипертермия сама по себе вызывала 10–20% угнетение роста культуры клеток. У всех исследованных химиотерапевтических препаратов отмечали эффект усиления при повышенной температуре. Коэффициент теплового усиления в отношении клеточной пролиферации для оксалиплатина, винорельбина, карбоплатина и ифосфамида превысил 4,0, для доксорубицина и гемцитабина — 2,0. Коэффициент теплового усиления в отношении гибели клеток не превышал 1,4. Выводы: синергизм гипертермии и химиотерапевтических препаратов продемонстрирован для оксалиплатина, винорельбина, карбоплатина, ифосфамида, в меньшей степени — для доксорубицина и гемцитабина. Усиление цитостатического эффекта противоопухолевых препаратов под действием гипертермии было более выраженным, чем их цитотоксического эффекта. Ключевые слова: гипертермия, противоопухолевые препараты, клетки HeLa, коэффициент теплового усиления. Copyright © Experimental Oncology, 2008

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