白术内酯-1通过JNK-pSmad3L-c-Myc信号通路在体内和体外抗胆囊癌活性研究

发布时间：2018-03-03 21:04

本文选题：白术内酯-1(ATR-1)　切入点：胆囊癌　出处：《山西医科大学》2017年硕士论文　论文类型：学位论文

【摘要】：目的:胆囊癌发病率居消化系统第六位,是最频繁多见的胆道恶性肿瘤,侵袭程度高,预后差。从白术中提取的白术内酯-1(ATR-1)作为一种在中国广泛使用的中草药,在膀胱癌等多种肿瘤细胞中表现出潜在的抗肿瘤活性。然而,很少见白术内酯-1对胆囊癌细胞的研究文献报道。本研究的目的主要是探讨ATR-1对胆囊癌细胞(NOZ和EHGB-1细胞)的增殖影响以及其潜在的分子机制,为ATR-1可能作为新型抗胆囊癌化疗药物提供实验数据和支撑。方法:在本次研究中,我们通过MTT、克隆形成实验研究了ATR-1对胆囊癌细胞株NOZ和EHGB-1细胞的增殖效应,使用Annexin-V/PI双重染色实验、Hoechest33342染色实验探讨ATR-1对胆囊癌细胞株的凋亡效应以及流式细胞学研究细胞周期实验,并采用Western blotting实验研究了ATR-1发挥抗胆囊癌作用的潜在分子机制;同时采用裸鼠负荷实验探讨了ATR-1对体内胆囊癌的抑制作用。结果:ATR-1根据剂量依赖方式促进NOZ和EHGB-1的凋亡、诱导周期趋于阻滞在G0/G1期,从而对胆囊癌细胞发生抗增殖效应。在裸鼠负荷瘤实验中,相比空白对照组,ATR-1药物浓度越大(在安全范围内),裸鼠皮下移植瘤的体积和重量越小。结论:ATR-1在体内和体外均能抑制胆囊癌细胞增殖,发挥抗肿瘤效应,有望成为胆囊癌辅助化疗中的新型药物。
[Abstract]:Objective: the incidence of gallbladder carcinoma is ranked 6th in the digestive system. It is the most frequent malignant tumor of the biliary tract, with high invasion and poor prognosis. Atractylodes macrocephala-1 ATR-1 extracted from macrocephala is widely used as a Chinese herbal medicine in China. It shows potential antitumor activity in many kinds of tumor cells, such as bladder cancer. However, The present study is to investigate the effect of ATR-1 on the proliferation of gallbladder cancer cells (Noz and EHGB-1 cells) and its potential molecular mechanism. Methods: in this study, we studied the effect of ATR-1 on the proliferation of NOZ and EHGB-1 cells. Annexin-V/PI double staining and Hoechest33342 staining were used to investigate the apoptotic effect of ATR-1 on gallbladder cancer cell line and the cell cycle test by flow cytometry. The potential molecular mechanism of ATR-1 's anti-gallbladder carcinoma was studied by Western blotting assay. The inhibitory effect of ATR-1 on gallbladder carcinoma in vivo was also investigated by using nude mice load test. Results: the apoptosis of NOZ and EHGB-1 was promoted by the dose dependent manner, and the induced cycle tended to be blocked at the G _ 0 / G _ 1 phase. Thus, the anti-proliferative effect on gallbladder cancer cells was observed in nude mice. Compared with the blank control group, the higher the concentration of ATR-1 was (within the safe range), the smaller the volume and weight of the tumor. Conclusion: in vivo and in vitro, the proliferation of gallbladder cancer cells can be inhibited and the antitumor effect of the tumor can be played by the control group. It is expected to be a new drug in adjuvant chemotherapy for gallbladder carcinoma.
【学位授予单位】：山西医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R735.8

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