Istomin Yu P, Zhavrid E A, Alexandrova E N, Sergeyeva O P, Petrovich S V
N.N. Alexandrov Research Institute of Oncology and Medical Radiology, Minsk 223040, Belarus.
Exp Oncol. 2008 Mar;30(1):56-9.
To evaluate in vitro the influence of elevated temperature (42 degrees C for 60 min) on the action of anticancer drugs doxorubicin, vinorelbine, carboplatin, ifosfamide, etoposide, oxaliplatin, docetaxel and gemcitabine.
HeLa tumor cell cultures, 24h after seeding, were incubated for 60 min with different concentrations of chemotherapeutical drugs at a temperature of 37 degrees C or 42 degrees C. 48 h later the number of viable cells in the flasks were counted using trypan-blue exclusion on a hemacytometer.
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.
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.
在体外评估高温(42℃,60分钟)对阿霉素、长春瑞滨、卡铂、异环磷酰胺、依托泊苷、奥沙利铂、多西他赛和吉西他滨等抗癌药物作用的影响。
接种后24小时的HeLa肿瘤细胞培养物,在37℃或42℃下用不同浓度的化疗药物孵育60分钟。48小时后,使用血细胞计数器通过台盼蓝排斥法对培养瓶中的活细胞数量进行计数。
单纯热疗仅导致细胞培养物生长抑制10 - 20%。所有使用的化疗药物在高温下均表现出剂量增强效应。奥沙利铂、长春瑞滨、卡铂和异环磷酰胺的细胞增殖热增强比超过4,阿霉素和吉西他滨超过2。细胞死亡的热增强比不超过1.4。
奥沙利铂、长春瑞滨、卡铂、异环磷酰胺以及程度稍轻的阿霉素和吉西他滨,均明确显示出热疗与化疗药物的协同作用。热疗对抗癌药物细胞生长抑制作用的增强比其细胞毒性作用更为显著。