Department of General Surgery, Xinhua Hospital Affiliated to Shanghai Jiao Tong University School of Medicine, Shanghai, China.
Shanghai Key Laboratory of Biliary Tract Disease Research, Shanghai, China.
Acta Biochim Biophys Sin (Shanghai). 2019 Jun 20;51(6):607-614. doi: 10.1093/abbs/gmz041.
Gallbladder carcinoma (GBC) is the most common and aggressive cancer of the biliary tract. Liensinine has been proved to have hypotensive effect. However, the effect of liensinine on GBC is still unknown. The aim of this study is to investigate the effect and mechanism of liensinine in human GBC cells. Cell viability assay and colony formation assay were performed to assess cell growth and proliferation. Flow cytometry analysis was used to investigate cell cycle apoptosis in vitro. Hoechst 33342 staining was also used to evaluate cell apoptosis. Western blot analysis was used to determine the expression of proteins corresponding to the related cell cycle and apoptosis. The effect of liensinine treatment in vivo was experimented with xenografted tumors. We found that liensinine significantly inhibited the growth of GBC cells both in vivo and in vitro. In vitro, cell growth and proliferation were significantly suppressed by liensinine in a dose- and time-dependent manner. In vivo, liensinine inhibited tumor growth. Liensinine could induce GBC cells G2/M phase arrest by up-regulating the levels of Cyclin B1 and CDK1 proteins. Liensinine also affected GBC cell cycle progression and induced apoptosis by down-regulating phosphorylated protein kinase B (AKT), phosphorylated protein kinase B (p-AKT), phosphatidylinositol 3-kinase (PI3K), and Zinc finger X-chromosomal protein (ZFX) proteins. Liensinine induced G2/M arrest and apoptosis in gallbladder cancer, suggesting that liensinine might represent a novel and effective agent against gallbladder cancer.
胆囊癌（GBC）是胆道最常见和最具侵袭性的癌症。莲心碱已被证明具有降压作用。然而，莲心碱对 GBC 的作用尚不清楚。本研究旨在探讨莲心碱对人 GBC 细胞的作用及其机制。细胞活力测定和集落形成测定用于评估细胞生长和增殖。流式细胞术分析用于体外研究细胞周期凋亡。Hoechst 33342 染色也用于评估细胞凋亡。Western blot 分析用于确定与细胞周期和凋亡相关的蛋白质表达。用异种移植肿瘤进行了莲心碱治疗的体内效应实验。我们发现莲心碱在体内和体外均显著抑制 GBC 细胞的生长。体外，莲心碱以剂量和时间依赖的方式显著抑制细胞生长和增殖。体内，莲心碱抑制肿瘤生长。莲心碱通过上调细胞周期蛋白 B1 和 CDK1 蛋白水平诱导 GBC 细胞 G2/M 期阻滞。莲心碱还通过下调磷酸化蛋白激酶 B（AKT）、磷酸化蛋白激酶 B（p-AKT）、磷酸肌醇 3-激酶（PI3K）和锌指 X 染色体蛋白（ZFX）蛋白来影响 GBC 细胞周期进程并诱导细胞凋亡。莲心碱诱导胆囊癌细胞 G2/M 期阻滞和凋亡，表明莲心碱可能是一种针对胆囊癌的新型有效药物。
