We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Inhibition of PI3K/Akt partially leads to the inhibition of PrP<sup>C</sup>-induced drug resistance in gastric cancer cells.
- Authors
Jie Liang; Fulin Ge; Changcun Guo; Guanhong Luo; Xin Wang; Guohong Han; Dexin Zhang; Jianhong Wang; Kai Li; Yanglin Pan; Liping Yao; Zhanxin Yin; Xuegang Guo; Kaichun Wu; Jie Ding; Daiming Fan
- Abstract
Cellular prion protein (PrPC), a glycosyl-phosphatidylinositol-anchored membrane protein with unclear physiological function, was previous found to be upregulated in adriamycin (ADR)-resistant gastric carcinoma cell line SGC7901/ADR compared to its parental cell line SGC7901. Overexpression of PrPC in gastric cancer has certain effects on drug accumulation through upregulation of P-glycoprotein (P-gp), which is suggested to play an important role in determining the sensitivity of tumor cells to chemotherapy and is linked to activation of the phosphatidylinositol-3-kinase/Akt (PI3K/Akt) pathway. In the present study, we further investigate the role of the PI3K/Akt pathway in PrPC-induced multidrug-resistance (MDR) in gastric cancer. Immunohistochemistry and confocal microscope detection suggest a positive correlation between PrPC and phosphorylated Akt (p-Akt) expression in gastric cancer. Using established stable PrPC transfectant cell lines, we demonstrated that the level of p-Akt was increased in PrPC-transfected cells. Inhibition of PrPC expression by RNA interference resulted in decreased p-Akt expression. Inhibition of the PI3K/Akt pathway by one of its specific inhibitors, LY294002, or by Akt small interfering RNA (siRNA) resulted in decreased multidrug resistance of SGC7901 cells, partly through downregulation of P-gp induced by PrPC. Taken together, our results suggest that PrPC-induced MDR in gastric cancer is associated with activation of the PI3K/Akt pathway. Inhibition of PI3K/Akt by LY2940002 or Akt siRNA leads to inhibition of PrPC-induced drug resistance and P-gp upregulation in gastric cancer cells, indicating a possible novel mechanism by which PrPC regulates gastric cancer cell survival.
- Subjects
CANCER cells; STOMACH cancer; DRUG resistance; IMMUNOHISTOCHEMISTRY; RNA
- Publication
FEBS Journal, 2009, Vol 276, Issue 3, p685
- ISSN
1742-464X
- Publication type
Article
- DOI
10.1111/j.1742-4658.2008.06816.x