BACKGROUND/AIMS: Ras homologue A (RhoA) plays a crucial role in the proliferation, apoptosis,adhesion and migration of gastric cancer cells. Rho associated kinase (ROCK) is an effector protein of RhoA. METHODOLOGY: In the present study, RhoA activity was inhibited by siRNA targeting RhoA andY-27632, an inhibitor of ROCK, and the role of RhoA/ROCK signaling pathway in the apoptosis of gastric cancer cells was investigated. RESULTS: RNAi of RhoA inhibited the survival and promoted the apoptotic of AGS cells. RhoA RNAi caused an obvious decrease of ROCK1 expression but an increase of caspase-3/cleaved-caspase-8. Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the apoptosis. CONCLUSIONS: We speculate that RhoA/ROCK signaling pathway plays an important role in the regulation of apoptosis of gastric cancer, and to inhibit this pathway may promote the apoptosis of cancer cells. Thus, inhibition of RhoA/ROCK signaling pathway may become a novel target in the treatment of gastric cancer.
BACKGROUND/AIMS: Ras homologue A (RhoA) plays a crucial role in the proliferation, apoptosis,adhesion and migration of gastric cancer cells. Rho associated kinase (ROCK) is an effector protein of RhoA. METHODOLOGY: In the present study, RhoA activity was inhibited by siRNA targeting RhoA andY-27632, an inhibitor of ROCK, and the role of RhoA/ROCK signaling pathway in the apoptosis of gastric cancer cells was investigated. RESULTS: RNAi of RhoA inhibited the survival and promoted the apoptotic of AGS cells. RhoA RNAi caused an obvious decrease of ROCK1 expression but an increase of caspase-3/cleaved-caspase-8. Inhibition of ROCK by Y-27632 inhibited the activity of RhoA and promoted the apoptosis. CONCLUSIONS: We speculate that RhoA/ROCK signaling pathway plays an important role in the regulation of apoptosis of gastric cancer, and to inhibit this pathway may promote the apoptosis of cancer cells. Thus, inhibition of RhoA/ROCK signaling pathway may become a novel target in the treatment of gastric cancer.
Authors: Namrata Setia; Agoston T Agoston; Hye S Han; John T Mullen; Dan G Duda; Jeffrey W Clark; Vikram Deshpande; Mari Mino-Kenudson; Amitabh Srivastava; Jochen K Lennerz; Theodore S Hong; Eunice L Kwak; Gregory Y Lauwers Journal: Mod Pathol Date: 2016-04-01 Impact factor: 7.842