Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells.
Oleanolic acid induces mitochondrial-dependent apoptosis and G0/G1 phase arrest in gallbladder cancer cells.
复制标题
齐墩果酸诱导胆囊癌细胞线粒体依赖性细胞凋亡和 G0/G1 期停滞
DOI：
10.2147/dddt.s84448
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发表时间：
2015
期刊：
影响因子：
--
通讯作者：
Liu YB
中科院分区：
文献类型：
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作者：
Li HF;Wang XA;Xiang SS;Hu YP;Jiang L;Shu YJ;Li ML;Wu XS;Zhang F;Ye YY;Weng H;Bao RF;Cao Y;Lu W;Dong Q;Liu YB
齐墩果酸 (OA) 是一种天然存在的三萜类化合物，在许多肿瘤细胞系中表现出潜在的抗肿瘤活性。胆囊癌是胆道最常见的恶性肿瘤，是一种侵袭性极强的肿瘤，预后极差。不幸的是，OA 对胆囊癌的影响尚不清楚。在这项研究中，我们研究了OA对胆囊癌细胞的影响及其潜在机制。 MTT和集落形成实验结果表明，OA对胆囊癌细胞增殖的抑制作用呈剂量依赖性和时间依赖性。流式细胞术检测显示 GBC-SD 和 NOZ 细胞发生凋亡和 G0/G1 期停滞。蛋白质印迹分析和线粒体膜电位测定表明 OA 通过线粒体凋亡途径发挥作用。此外，该药物还能抑制携带皮下NOZ肿瘤异种移植物的裸鼠的肿瘤生长。这些数据表明OA通过调节细胞凋亡和细胞周期过程来抑制胆囊癌细胞的增殖。因此，OA可能是胆囊癌辅助化疗的一种有前途的药物。
Oleanolic acid (OA), a naturally occurring triterpenoid, exhibits potential antitumor activity in many tumor cell lines. Gallbladder carcinoma is the most common malignancy of the biliary tract, and is a highly aggressive tumor with an extremely poor prognosis. Unfortunately, the effects of OA on gallbladder carcinoma are unknown. In this study, we investigated the effects of OA on gallbladder cancer cells and the underlying mechanism. The results showed that OA inhibits proliferation of gallbladder cancer cells in a dose-dependent and time-dependent manner on MTT and colony formation assay. A flow cytometry assay revealed apoptosis and G0/G1 phase arrest in GBC-SD and NOZ cells. Western blot analysis and a mitochondrial membrane potential assay demonstrated that OA functions through the mitochondrial apoptosis pathway. Moreover, this drug inhibited tumor growth in nude mice carrying subcutaneous NOZ tumor xenografts. These data suggest that OA inhibits proliferation of gallbladder cancer cells by regulating apoptosis and the cell cycle process. Thus, OA may be a promising drug for adjuvant chemotherapy in gallbladder carcinoma.