摘要
目的:探索中医解毒法协同化疗在结肠癌辅助治疗阶段的优化治疗模式,并初步探讨作用机制。方法:①皮下接种CT26细胞于120只BALB/c小鼠建立移植瘤模型,分为6组:提前干预组、延后干预组、维持干预组、单纯中药组、单纯化疗组、模型对照组,每组20只。②取6组移植瘤模型小鼠每组10只,治疗后观察生存期,绘制生存曲线。③免疫组化(SP法)及Western Blot法检测瘤体天冬氨酸特异性胱氨酸蛋白酶-3(Caspase-3)、Rho相关的卷曲蛋白激酶2(ROCK2)、哺乳动物雷帕霉素靶蛋白(mTOR)表达水平。结果:①生存期:提前干预组、延后干预组、单纯化疗组小鼠的平均生存期和中位生存期显著延长,和模型对照组相比,差异有统计学意义(P<0.05);②免疫组化结果:各治疗组Caspase-3表达较模型对照组均有上升,提前干预组、延后干预组、维持干预组高于单药治疗组,提前干预组、延后干预组、单纯化疗组和模型对照组比较差异有统计学意义(P<0.05);各治疗组mTOR、ROCK2表达量均有下降,其中提前干预组、延后干预组和模型对照组比较差异有统计学意义(P<0.05)。③Western Blot结果:提前干预组、延后干预组及单纯化疗组能上调Caspase-3表达,提前干预组、延后干预组和模型对照组比较差异有统计学意义(P<0.05);各治疗组均能够下调ROCK2表达,提前干预组、延后干预组、单纯中药组和模型对照组比较差异有统计学意义(P<0.05);各治疗组均能够下调mTOR表达,提前干预组、延后干预组、单纯化疗组和模型对照组比较差异有统计学意义(P<0.05)。结论:①化疗前应用解毒法能延长总生存期,起到减毒增效的作用。单独运用中医解毒法可以缓解疾病进展,延长生存时间,达到"带瘤生存"。②中医解毒法协同化疗能延长生存期的作用机制可能与上调肿瘤促凋亡蛋白Caspase-3表达,下调肿瘤侵袭转移相关蛋白ROCK2表达,下调增殖相关蛋白mTOR表达有关。
Objective： To investigate the optimum combination of disintoxication and chemotherapy in auxiliary treatment phase on colon cancer xenografts in mice, elucidate the potential mechanism of Chinese herbal for adjuvant chemotherapy. Methods： ①Colon cancer cell line CT26 was injected subcutaneously on 120 BALB/c mice to establish colon cancer xenografts model, they were randomly divided into 6 groups： pre-intervention group, post-intervention group, maintain intervention group, herbal only group, chemotherapy only group, model control, 20 in each group. ②10 BALB/c mice from each groups were chosen to observe survival time and draw the survival curves after treatment. ③Detecting the expression level of Caspase-3, ROCK2, roTOR in tumor tissue by IHC （SP method） and Western Blot. Results： ①Overall survival： Compared withmodel control group, the mean survival time and median survival time were significantly extended in pre-intervention group, herbal only group. The difference was statistical significance （P〈0.05）; ②IHC： The expression of Caspase-3 in all treatment groups was increased, with dramatic increase in two therapy combination group. Compared with model control group, pre- intervention group, post-intervention group and chemotherapy group had statistical significance （P〈0.05）; mTOR、ROCK2 level in pre-intervention group and post-intervention group declined and had statistical significance compared with model control group （P〈0.05）. ③Western Blot： The expression of Caspase-3 was increase in two therapy combination group and chemotherapy group, within which pre-intervention group and post-intervention group had statistical significance compared with model control group （P〈0.05）; the expression of ROCK2, mTOR decreased in each treatment groups, ROCK2 level in pre-intervention group, post- intervention group and herbal only group declined and had statistical significance compared with model control group （P〈0.05）; mTOR level in pre-intervention group, post-intervention group and chemotherapy group declined and had statistical significance compared with model control group （P〈0.05）. Conclusion： ①Appling detoxicating therapy before chemotherapy increased overall survival, with the function of enhancing efficiency and reducing the toxic side. Appling single detoxicating therapy slowed the progression of disease, increased survival time and realized the state of ＇survival with tumor＇. ②The mechanism of the combination of detoxicating therapy and chemotherapy increased overall survival perhaps related to increasing Caspase-3 which inducing apoptin and decreasing expression of ROCK2, mTOR implicated in tumor invasion and metastasis and proliferation.
出处
《中华中医药杂志》
CAS
CSCD
北大核心
2013年第6期1714-1718,共5页
China Journal of Traditional Chinese Medicine and Pharmacy
基金
国家公益性行业科研专项项目(No.200807018)
浙江省教育厅项目(No.Y201016272)~~
关键词
解毒法
结肠癌
优化治疗模式
总生存期
Disintoxication
Colon cancer
Optimum mode
Overall survival
