目的:研究热化疗对小细胞肺癌生长的影响及其可能的机制。方法:参考临床常用剂量,采用43℃加热联合120μg/L紫杉醇(热化联合组)、43℃加热联合120μg/L紫杉醇及20μmol/LJNK特异抑制剂SP600125(热化联合+SP600125组)、单纯43℃加热(单纯热疗组)、单纯使用120μg/L紫杉醇(单纯化疗组)处理H446细胞,以未处理的H446细胞作对照。应用四甲基偶氮唑盐比色法(MTT法)检测各处理方式下细胞增殖率的变化,通过Western印迹法检测JNK、磷酸化JNK(p-JNK)和HSP70的表达并对数据进行统计学分析。结果:热化联合组细胞增殖率低于对照组、单纯化疗、单纯热疗及热化联合+SP600125组(P〈0.05);p-JNK表达水平在热化联合组中表达明显增高(P〈0.05),但SP600125可抑制其表达,使热化联合+SP600125组细胞的增殖率相应增高(P〈0.05);HSP70在热化联合组的表达低于单纯热疗组(P〈0.05),细胞增殖率也发生了相应变化。结论:热疗可以明显增加紫杉醇对H446细胞生长的抑制作用,且这种作用可能是通过激活JNK信号转导通路或抑制HSP70的表达完成的。
Objective:To study the effect of thermo-chemotherapy on lung cancer and its possible mechanism. Methods: H446 cells were subjected to different thermo-chemotherapy strategies: 43℃ +Paclitaxel (120 μg/L, thermo-chemotherapy group), 43℃ +Paclitaxel (120 μg/L) + SP600125 (20 tLmol/L,JNK inhibitor) (thermo-chemotherapy+ SP600125 group), thermotherapy (43℃) group, and Paclitaxel ( 120 μg/L) group; untreated cells served as control. MTT assay was used to measure cell proliferation and Western blotting was used to examine the expression of JNK, p-JNK and HSP70 protein. Results: The proliferation rate of cells in the thermo-chemotherapy group was significantly lower than those in the other 3 groups (all P〈0.05). The expression of p-JNK was significantly increased in the thermo-chemotherapy group (P〈0.05) ; SP600125 inhibited the expression of p-JNK and the proliferation of cells in the thermo-chemotherapy+SP600125 group was elevated (P〈 0.05). The expression of HSP70 in the thermo-chemotherapy group was lower than that of the thermotherapy group (P〈 0.05). Conclusion: Thermotherapy can obviously promote the inhibitory effect of Paclitaxel chemotherapy against the growth of lung cancer cell line H446, probably through activating JNK pathway or inhibiting expression of HSP70 protein.