RhoGDI2 up-regulates P-glycoprotein expression via Rac1 in gastric cancer cells

Cancer Cell International

Xiaohua Wu²  Bingya Liu¹  Zhong Zheng² 

[1] 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;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

关键词: Rac1;    P-gp;    Gastric cancer;    Multidrug resistance;    RhoGDI2;   

Others  :  1217745
DOI  :  10.1186/s12935-015-0190-4

 received in 2014-12-10, accepted in 2015-03-28,  发布年份 2015

【 摘 要 】

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.

【 授权许可】

   
2015 Zheng et al.; licensee BioMed Central.

【 图 表 】

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