Department of Microbiology/Research Institute of Life Science, College of Natural Sciences, Gyeongsang National University, Jinju 660-701, Republic of Korea.
Biochem Biophys Res Commun. 2011 Oct 28;414(3):575-80. doi: 10.1016/j.bbrc.2011.09.121. Epub 2011 Oct 1.
Rho GDP dissociation inhibitor 2 (RhoGDI2) is a regulator of the Rho family GTPases. Recent work from our laboratory suggests that RhoGDI2 expression potentially enhances resistance to cisplatin as well as promotes tumor growth and malignant progression in gastric cancer. In this study, we demonstrate that phospholipase C-gamma (PLCγ) is required for RhoGDI2-mediated cisplatin resistance and cancer cell invasion in gastric cancer. The levels of phosphorylated PLCγ are markedly enhanced in RhoGDI2-overexpressing SNU-484 cells and, by contrast, repressed in RhoGDI2-depleted MKN-28 cells. Depletion of PLCγ expression or inhibition of its activity not only significantly increases cisplatin-induced apoptosis but also suppresses the invasive ability of RhoGDI2-overexpressing SNU-484 cells. Taken together, our results suggest that PLCγ plays a key role in RhoGDI2-mediated cisplatin resistance and cell invasion in gastric cancer cells.
Rho GDP 解离抑制剂 2（RhoGDI2）是 Rho 家族 GTPases 的调节剂。我们实验室的最新研究表明，RhoGDI2 的表达可能增强了胃癌对顺铂的耐药性，并促进了肿瘤生长和恶性进展。在这项研究中，我们证明了磷脂酶 C-γ（PLCγ）是 RhoGDI2 介导的胃癌顺铂耐药和癌细胞侵袭所必需的。在 RhoGDI2 过表达的 SNU-484 细胞中，磷酸化 PLCγ 的水平明显增强，而在 RhoGDI2 耗尽的 MKN-28 细胞中则受到抑制。PLCγ 表达的缺失或其活性的抑制不仅显著增加了顺铂诱导的细胞凋亡，而且还抑制了 RhoGDI2 过表达的 SNU-484 细胞的侵袭能力。综上所述，我们的结果表明，PLCγ 在 RhoGDI2 介导的胃癌细胞顺铂耐药和细胞侵袭中发挥关键作用。
