Activation of phospholipase C-gamma l and translocation of phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase contribute to GL-V9-induced apoptosis in human gastric cancer cells

作者：Zhaol, Kai; Li, Guojun; Yao, Yuyuan; Zhou, Yuxin; Li, Zhiyu; Guo, Qinglong^*; Lu, Na^*

来源：Experimental Cell Research, 2017, 356(1): 8-19.

DOI：10.1016/j.yexcr.2017.03.063

• GL-V9
• Gastric cancer
• Apoptosis
• Ca2+ release

Gastric cancer is the most common type of tumor in developing countries and the fourth most frequently diagnosed cancer worldwide. Here, we demonstrated the apoptotic effects of GL-V9 on several human gastric cancer cells and selected MGC-803 cells to uncover the underlying mechanism. GL-V9 elevated Bax/Bcl-2 ratio, abated mitochondrial membrane potential and triggered the onset of apoptotic execution in MGC-803 cells. Our research revealed that CHOP silencing could not inhibit apoptosis, neither could it block Ca2+ release, suggesting that GL-V9 -induced apoptosis was independent of CHOP. Furthermore, GL-V9 increased mitochondrial Ca2+ uptake through 1,4,5-triphosphate (IP3) receptor via the activation of phospholipase C-gamma l and the translocation of phosphatidylinositol-3,4,5-trisphosphate 3-phosphatase from nucleus to endoplasmic reticulum. Moreover, in-vivo studies indicated that GL-V9 exhibited significant MGC-803 xenografts regression in nude mice with low systemic toxicity. In conclusion, GL-V9 could induce apoptosis in gastric cancer cells, and would be a promising therapeutical agent against gastric cancer.

• 出版日期2017-7-1
• 单位中国药科大学