Matrine Inhibits Proliferation and Induces Apoptosis of Pancreatic Cancer Cells in Vitro and in Vivo

作者：Tianyou Liu, Yan Song, Hua Chen, Shangha Pan, Xueying Sun · 发表于：Biological and Pharmaceutical Bulletin · 年份：2010 · DOI：10.1248/bpb.33.1740 · 被引用次数：103 · 研究领域：Bioactive natural compounds、Retinoids in leukemia and cellular processes、Bioactive Compounds and Antitumor Agents

Matrine, an alkaloid extracted from a Chinese herb, Sophora flavescens AIT., has exhibited anti-proliferative and pro-apoptotic abilities against various types of cancer cells. This study aims to investigate its anti-cancer activity and underlying mechanisms in human pancreatic cancer cells in vitro and in vivo. Human BxPC-3 and PANC-1 pancreatic cancer cells, and human HL-7702 liver cells were incubated with matrine at different concentrations. Cell viability was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, and cell apoptosis, by flow cytometry. Subcutaneous BxPC-3 xenograft tumors were established in nude BALB/c mice, and matrine was intraperitoneally (i.p.) administered. The tumors were monitored and harvested. Tumor sections were immunostained with an anti-Ki-67 antibody (Ab) to examine cell proliferation, or stained with terminal deoxynucleotidyl transferase mediated deoxyuridine triphosphate (dUTP) nick-end labeling (TUNEL) to evaluate in situ cell apoptosis. The expression of proliferating cell nuclear antigen (PCNA) and several apoptosis-related proteins in cells and tumor tissues were evaluated by Western blot analysis. In in vitro assays, matrine inhibited cell viability by downregulating the expression of PCNA, and induced cell apoptosis by reducing the ratio of Bcl-2/Bax, upregulating Fas, and increasing activation of caspases-8,-3 and -9, in a dose-dependent manner. Administration of matrine inhibited tumor growth in a dos...