JNK通路及HSP70在热化疗抑制人小细胞肺癌细胞生长中的作用
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国家自然科学基金(30571552);郑州市2006年度科技发展计划(19-153).


Role of JNK pathway and HSP70 in thermochemotherapy of lung cancer
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Supported by National Natural Science Foundation of China(30571552) and Program of Science and Technology Development of Zhengzhou Municipal Government,2006(19153).

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    摘要:

    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120 μg/L紫杉醇(热化联合组)、43℃加热联合120 μg/L紫杉醇及20 μmol/L JNK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120 μg/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。

    Abstract:

    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 μmol/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.

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  • 收稿日期:2007-10-28
  • 最后修改日期:2008-01-13
  • 录用日期:2008-01-28
  • 在线发布日期: 2008-01-31
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