Zhang Shujun, Cheng Binglin, Li Hali, Xu Wei, Zhai Bo, Pan Shangha, Wang Lei, Liu Ming, Sun Xueying
Department of Pathology, The Fourth Affiliated Hospital of Harbin Medical University, Harbin, 150001, China.
Mol Biol Rep. 2014;41(4):2101-8. doi: 10.1007/s11033-014-3059-z. Epub 2014 Jan 23.
The present study has investigated the anti-tumor activity and the underlying mechanisms of matrine on human colon cancer LoVo cells. Matrine inhibited the proliferation of the cells in dose- and time-dependent manners. The concentration required for 50 % inhibition (IC50) was 1.15, 0.738, and 0.414 mg/ml, when cell were incubated with matrine for 24, 48, and 72 h, respectively. Matrine induced cell cycle arrest at G1 phase by downregulating cyclin D1 and upregulating p27 and p21. Matrine induced cell apoptosis by reducing the ratio of Bcl-2/Bax and increasing the activation of caspase-9 in a dose-dependent manner. Matrine displayed its anti-tumor activity by inactivating Akt, the upstream factor of the above proteins. Matrine significantly reduced the protein levels of pAkt, and increased the protein levels of other downstream factors, pBad and pGSK-3β. Specific inhibition of pAkt induced cell apoptosis, and synergized with matrine to inhibit the proliferation of LoVo cells; whereas activation of Akt neutralized the inhibitory effect of matrine on cell proliferation. The present study has demonstrated that matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway, indicating matrine may be a potential anti-cancer agent for colon cancer.
本研究探讨了苦参碱对人结肠癌LoVo细胞的抗肿瘤活性及其潜在机制。苦参碱以剂量和时间依赖性方式抑制细胞增殖。当细胞分别与苦参碱孵育24、48和72小时时,50%抑制所需的浓度(IC50)分别为1.15、0.738和0.414mg/ml。苦参碱通过下调细胞周期蛋白D1并上调p27和p21诱导细胞周期停滞在G1期。苦参碱通过降低Bcl-2/Bax比值并以剂量依赖性方式增加caspase-9的活化诱导细胞凋亡。苦参碱通过使上述蛋白的上游因子Akt失活发挥其抗肿瘤活性。苦参碱显著降低pAkt的蛋白水平,并增加其他下游因子pBad和pGSK-3β的蛋白水平。特异性抑制pAkt诱导细胞凋亡,并与苦参碱协同抑制LoVo细胞的增殖;而Akt的激活则抵消了苦参碱对细胞增殖的抑制作用。本研究表明,苦参碱通过使Akt通路失活抑制人结肠癌LoVo细胞的增殖并诱导其凋亡,表明苦参碱可能是一种潜在的结肠癌抗癌药物。