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  • VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance.

VEGF-C mediates RhoGDI2-induced gastric cancer cell metastasis and cisplatin resistance.

International journal of cancer (2014-03-04)
Hee Jun Cho, In-Kyu Kim, Sun-Mi Park, Kyoung Eun Baek, In-Koo Nam, Seung-Ho Park, Ki-Jun Ryu, Jungil Choi, Jinhyun Ryu, Soon-Chan Hong, Sang-Ho Jeong, Young-Joon Lee, Gyung-Hyuck Ko, Jae Kim, Chang Won Lee, Sang Soo Kang, Jiyun Yoo

Rho GDP dissociation inhibitor 2 (RhoGDI2) expression is correlated with tumor growth, metastasis and chemoresistance in gastric cancer. However, the mechanisms by which RhoGDI2 promotes tumor cell survival and metastasis remain unclear. In this study, we clearly demonstrate that RhoGDI2 upregulates VEGF-C expression and RhoGDI2 expression is positively correlated with VEGF-C expression in human gastric tumor tissues as well as parental gastric cancer cell lines. VEGF-C depletion suppressed RhoGDI2-induced gastric cancer metastasis and sensitized RhoGDI2-overexpressing cells to cisplatin-induced apoptosis in vitro and in vivo. Secreted VEGF-C enhanced gastric cancer cell invasion and conferred cisplatin resistance to RhoGDI2-overexpressing cells. We also show that RhoGDI2 positively regulates Rac1 activity in gastric cancer cells. Inhibition of Rac1 expression suppressed RhoGDI2-induced VEGF-C expression, and this inhibition was associated with decreased invasiveness and increased sensitivity to cisplatin in RhoGDI2-overexpressing cells. Our results indicate that RhoGDI2 might be a potential therapeutic target for simultaneously reducing metastasis risk and enhancing chemotherapy efficacy in gastric cancer.

Product Number
Product Description

cis-Diamineplatinum(II) dichloride, ≥99.9% trace metals basis
cis-Diammineplatinum(II) dichloride, crystalline
Cisplatin, European Pharmacopoeia (EP) Reference Standard