Effect of Adhesion Molecular CD146 on Apoptosis of Ovarian Cancer Cell Induced by Vorinostat
MA Xiao-li
LIU Yu-sheng
YAN Xi-yun
GUO Yin-shu
DUAN Hua
MA Ding
Abstract：Objective:To investigate the effect of adhesion molecular CD146 expression on apoptosis of ovarian cancer cells induced by Vorinostat. Methods:CD146 expression levels in A2780 and SKOV3 cells were detected after Vorinostat treatment by Real-time PCR and Western blot. The effect of CD146 mAb AA98 on cell apoptosis and colony-forming ability under Vorinostat treatment by FACS and Soft agar colony-forming assay. The synergistic effect of Vorinostat and AA98 was analyzed by gold formula method. Comparison of effect on AKT/mTOR signaling pathway and the downstream molecular between ovarian cancer cells treated by Vorinostat alone or plus with AA98. Results:CD146 was significantly induced by Vorinostat in ovarian cancer cells. Upregulation of CD146 is closely related to chemosensitivity. Combined Vorinostat and AA98 significantly improved cell apoptotic rate and ablated cancer colony formation. The difference was statistically significant ( P<0.05). The synergistic effect after treatment with a combination of Vorinostat with AA98 was proved by gold formula method. AA98 could reduce the activation of AKT/mTOR signaling pathway caused by Vorinostat and could decrease the p-AKT ,p-4E-BP1,p-S6K1 protein levels in ovarian cancer cells (P<0.05). Conclusions:Vorinostat significantly induced the expression of CD146, which might decrease the chemosensitivity of ovarian cancer cells. CD146 mAb may reverse and inhibit the activation of AKT/mTOR signaling pathway caused by Vorinostat and substantially enhance killing of ovarian cancer cells. The two drugs have obvious synergistic antitumor effects.
Keywords：Ovarian neoplasmsAntigensCD146Antineoplastic agentsVorinostatApoptosisSynergistic effect
Publication Date：2016-01-01
Online Publishing Date：2025-08-15(First online date of this platform, not the publication date of the document)
Pages：5( 690-694 )