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| 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 |
| 王琳1,高姗1,张瑞芳2,吴卫东1，3,吴逸明1* |
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| (1.郑州大学公共卫生学院职业卫生与职业病学教研室，郑州 450052;2.新乡医学院公共卫生学系，新乡 453003;3.The Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599,USA) |
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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（pJNK）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）；pJNK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。 |
| 关键词: 肺肿瘤 H446细胞 JNK丝裂原活化蛋白激酶类 热休克蛋白质70 温热疗法 药物疗法 细胞增殖 |
| DOI：10.3724/SP.J.1008.2008.00142 |
| 投稿时间：2007-10-28修订日期：2008-01-13 |
| 基金项目:国家自然科学基金(30571552);郑州市2006年度科技发展计划(19-153). |
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| Role of JNK pathway and HSP70 in thermo chemotherapy of lung cancer |
| WANG Lin1,GAO Shan1,ZHANG Rui-fang2,WU Wei-dong1，3,WU Yi-ming1* |
| (1.Department of Occupational Medicine, College of Public Health, Zhengzhou University, Zhengzhou 450052, China;2.Faculty of Public Health, Xinxiang Medical College, Xinxiang 453003, China;3.The Center for Environmental Medicine and Lung Biology, University of North Carolina, Chapel Hill, North Carolina 27599,USA) |
| Abstract: |
| Objective：To study the effect of thermochemotherapy on lung cancer and its possible mechanism. Methods: H446 cells were subjected to different thermochemotherapy strategies: 43℃+Paclitaxel (120 μg/L,thermochemotherapy group), 43℃+Paclitaxel (120 μg/L)+SP600125 (20 μmol/L,JNK inhibitor) (thermochemotherapy+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, pJNK and HSP70 protein. Results: The proliferation rate of cells in the thermochemotherapy group was significantly lower than those in the other 3 groups (all P<0.05). The expression of pJNK was significantly increased in the thermochemotherapy group (P<0.05); SP600125 inhibited the expression of pJNK and the proliferation of cells in the thermochemotherapy+SP600125 group was elevated (P<0.05). The expression of HSP70 in the thermochemotherapy 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. |
| Key words: lung neoplasms H446 cells JNK mitogen activated protein kinases heat shock proteins 70 thermotherapy drug therapy cell proliferation |
