Department of General Surgery, Hainan Province People's hospital, 570311, China.
The department of Hepatopancreatobiliary Surgery, The 2nd Affliated Hospital of Hainan Medical University, 570000, China.
Biomed Pharmacother. 2017 Nov;95:324-330. doi: 10.1016/j.biopha.2017.08.029. Epub 2017 Sep 12.
The aim of this study is to explain effect and mechanism of Sophoridine to suppress Hepatocellular carcinoma in vitro and vivo.
In vitro experiment, the HepG2 cells were divided into 5 groups: 0μg/mL Sophoridine treated group (0 μg/mL group); 10μg/mL matrine treated group (10μg/mL group); 20μg/mL matrine treated group (20μg/mL group) and 10μg/mL Paclitaxel treated group (Positive drug group). Measuring the cell proliferation of difference groups by MTS assay; evaluating cell apoptosis of difference by flow cytometry; the cell invasion and migration abilities of difference HepG2 cells were measured by transwell and wound healing testing; measuring the relative proteins expression in difference groups. In vovo experiment, the nude mice were divided into 5 groups: 0μg/mL, 5μg/mL, 10μg/mL, 20μg/mL and Positive drug groups, after executing, taking the tumor tissue from nude mice of difference groups, measuring the tumor volume and weight; evaluating the PTEN protein expression in tumor tissue by Immunohistochemistry (IHC).
In the cell experiments, Compared with 0μg/mL group, cell proliferation rates were significantly reduced, cell aopotosis were significantly increased and invasion and wound healing abilities were significantly decreased in marine treated groups with dose-dependent (P<0.05, respectively). In the nude mice experiment, the tumor volume and weight of matrine treated groups were significantly decreased compared with 0 μg/mL group with dose-dependent (P<0.05, respectively). And the PTEN protein expression of Sophoridine treated groups were significantly decreased compared with 0μg/mL group with dose-dependent (P<0.05, respectively).
Sophoridine had anti-cance effects to suppress HepG2 activities by regulation PTEN/PI3K/AKT, Caspase-3/-9 and MMP-2/-9 signaling pathway.
本研究旨在解释苦参碱在体外和体内抑制肝癌的作用和机制。
体外实验将 HepG2 细胞分为 5 组：0μg/ml 苦参碱处理组（0μg/ml 组）；10μg/ml 苦参碱处理组（10μg/ml 组）；20μg/ml 苦参碱处理组（20μg/ml 组）和 10μg/ml 紫杉醇处理组（阳性药物组）。通过 MTS 法测定各组细胞增殖情况；采用流式细胞术评价细胞凋亡情况；通过 Transwell 和划痕实验测定各组 HepG2 细胞的侵袭和迁移能力；测定各组相对蛋白表达。体内实验将裸鼠分为 5 组：0μg/ml 组、5μg/ml 组、10μg/ml 组、20μg/ml 组和阳性药物组，处死裸鼠后取肿瘤组织，测量肿瘤体积和重量；采用免疫组织化学法（IHC）评价肿瘤组织中 PTEN 蛋白的表达。
在细胞实验中，与 0μg/ml 组相比，苦参碱处理组的细胞增殖率显著降低，细胞凋亡率显著升高，侵袭和迁移能力显著降低，且呈剂量依赖性（P<0.05，分别）。在裸鼠实验中，苦参碱处理组的肿瘤体积和重量均显著低于 0μg/ml 组，且呈剂量依赖性（P<0.05，分别）。苦参碱处理组的 PTEN 蛋白表达均显著低于 0μg/ml 组，且呈剂量依赖性（P<0.05，分别）。
苦参碱通过调节 PTEN/PI3K/AKT、Caspase-3/-9 和 MMP-2/-9 信号通路，发挥抑制 HepG2 活性的抗癌作用。
