title: RhoGDI2 up-regulates P-glycoprotein expression via Rac1 in gastric cancer cells.
abstract: Multidrug resistance (MDR) is a major clinical obstacle in treatment of gastric cancer. Previously, using 2D electrophoresis-mass spectrometry, we identified RhoGDI2 as a contributor to 5-FU resistance in colon cancer cells, and also confer gastric cancer cells resistance to 5-FU. Here, we reported RhoGDI2 also induced MDR in gastric cancer cell line (MKN-45). To explore the underlining mechanism, we detected the mRNA, protein expression, activity of P-glycoprotein (P-gp) in MKN-45 stably transfected with RhoGDI2 expressing or control vector. All the mRNA, protein level, activity were increased by 130%, 230%, 35% respectively after ectopic expression of RhoGDI2. RhoGDI2 was correlated with P-gp expression in gastric cancer tissues as detected by immunohistochemistry. To further study how RhoGDI2 up-regulates P-gp expression, we tested the activity of Rac1 in MKN-45/RhoGDI2 and MKN-45/GFP. Ectopic expression of RhoGDI2 increased Rac1 activity (P < 0.05). For more important, silencing of Rac1 expression by siRNA decreased P-gp expression to undetectable level. Overall, these findings suggest that RhoGDI2 up-regulates P-gp expression via Rac1 to induce MDR.
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032 People's Republic of China.
authors.forename: Zhong
authors.initials: Z
authors.lastname: Zheng
authors.affiliation: Department of Surgery, Shanghai Key Laboratory of Gastric Neoplasms, Shanghai Institute of Digestive Surgery, and Gastroenterology, Ruijin Hospital, Jiaotong University School of Medicine, Shanghai, China.
authors.forename: Bingya
authors.initials: B
authors.lastname: Liu
authors.affiliation: Department of Gynecologic Oncology, Fudan University Shanghai Cancer Center, Department of Oncology, Shanghai Medical College, Fudan University, 270 Dongan Road, Shanghai, 200032 People's Republic of China.
authors.forename: Xiaohua
authors.initials: X
authors.lastname: Wu
keywords: Gastric cancer; Multidrug resistance; P-gp; Rac1; RhoGDI2