Matrine inhibits proliferation and induces apoptosis of human colon cancer LoVo cells by inactivating Akt pathway

被引:56
|
作者
Zhang, Shujun [1 ]
Cheng, Binglin [2 ]
Li, Hali [3 ]
Xu, Wei [2 ]
Zhai, Bo [3 ]
Pan, Shangha [3 ]
Wang, Lei [4 ]
Liu, Ming [4 ]
Sun, Xueying [3 ]
机构
[1] Harbin Med Univ, Dept Pathol, Affiliated Hosp 4, Harbin 150001, Peoples R China
[2] Harbin Med Univ, Dept Integrated Med, Affiliated Hosp 1, Harbin 150001, Peoples R China
[3] Harbin Med Univ, Hepatosplen Surg Ctr, Dept Gen Surg, Affiliated Hosp 1, Harbin 150001, Peoples R China
[4] Harbin Med Univ, Dept Oncol, Affiliated Hosp 4, Harbin 150001, Peoples R China
关键词
Matrine; LoVo cells; Apoptosis; Cell cycle; Akt pathway; IN-VITRO; CARCINOMA-CELLS; UP-REGULATION; GROWTH; DEGRADATION; EXPRESSION; ROLES; VIVO;
D O I
10.1007/s11033-014-3059-z
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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-3 beta. 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.
引用
收藏
页码:2101 / 2108
页数:8
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