Zhang Ling, Zhu Shengtao, Shi Xuesen, Sha Weihong
Southern Medical University Guangzhou, China ; Department of Gastroenterology and Hepatology, Guangdong General Hospital, Guangdong Academy of Medical Sciences Guangzhou, China.
Department of Gastroenterology, Beijing Digestive Disease Center, Beijing Friendship Hospital Affiliated to Capital Medical University Beijing, China.
Int J Clin Exp Pathol. 2015 Aug 1;8(8):9097-104. eCollection 2015.
Colon cancer is the second most common cause of cancer-related death, indicating that some of its cancer cells are not eradicated by current therapies. The previous studies demonstrated that p66(Shc) protein, a member of Shc family, is highly expressed in colon cancer cells, but the role of p66(Shc) in the progress of colon cancer still unknown. In this study, we found that p66(Shc) highly expressed in colon cancer tissue and colon cancer cell line SW620 cells, HCT8 cells, HCT116 cells and CaCO2 cells. The silence of p66(Shc) in HCT8 cells reduced the proliferation and accelerated the apoptosis, in addition, the expression of pro-apoptotic proteins caspase-3, caspase-9, Bax was enhanced and the expression of anti-apoptotic protein Bcl-2 was declined. Moreover, the cell cycle arrest in G0/G1 phase after HCT8 cells treated with p66(Shc) siRNA. Furthermore, after HCT8 cells treated with p66(Shc) siRNA, the phosphorylation of PI3K and AKT was significantly suppressed, and the expression of Mdm-2, a downstream of AKT, was obviously prohibited, while the expression of p53 was enhanced. These results indicate that the silence of p66(Shc) in HCT8 cells inhibits the viability via PI3K/AKT/Mdm-2/p53 signaling pathway, it may provide a promising approach to prevent the progress of colon cancer cell.
结肠癌是癌症相关死亡的第二大常见原因，这表明其一些癌细胞未被当前疗法根除。先前的研究表明，Shc家族成员p66(Shc)蛋白在结肠癌细胞中高度表达，但p66(Shc)在结肠癌进展中的作用仍不清楚。在本研究中，我们发现p66(Shc)在结肠癌组织以及结肠癌细胞系SW620细胞、HCT8细胞、HCT116细胞和CaCO2细胞中高度表达。HCT8细胞中p66(Shc)的沉默降低了细胞增殖并加速了细胞凋亡，此外，促凋亡蛋白caspase-3、caspase-9、Bax的表达增强，抗凋亡蛋白Bcl-2的表达下降。此外，用p66(Shc) siRNA处理HCT8细胞后，细胞周期停滞在G0/G1期。此外，用p66(Shc) siRNA处理HCT8细胞后，PI3K和AKT的磷酸化被显著抑制，AKT下游的Mdm-2的表达明显受到抑制，而p53的表达增强。这些结果表明，HCT8细胞中p66(Shc)的沉默通过PI3K/AKT/Mdm-2/p53信号通路抑制细胞活力，这可能为预防结肠癌细胞进展提供一种有前景的方法。
