The roles of cadherin 17 in interleukin-10-induced invasion of gastric cancer cells

Abstract

Objective To explore the roles and mechanisms of Cadherin 17 (CDH17) in interleukin-10-induced invasion of gastric cancer cells. Methods We detected the invasion of MKN-45 gastric cancer cells induced by interleukin-10 through Transwell assay. CDH17 small interfering RNA (siRNA) was constructed and transfected in MKN-45 cells to inhibit CDH17 expression. We then compared the difference in cell invasion with or without CDH17 expression and detected the activation of corresponding signaling pathway by immunoblotting in response to interleukin-10. We additionally detected invasion of MKN-45 cell after inactivation of signaling by using its specific inhibitor. Results Western blotting and transwell assay revealed that interleukin-10 (100 ng/ml) significantly induced expression of CDH17 in MKN-45 cells (P=0.021) and promoted its invasion (10 250±1 500 vs. 2 750±450, P=0.019) as well as activated phosphoinositide-3-kinase (PI3K)/protein kinase B (Akt) signaling pathway (P=0.041). After successful inhibition of CDH17 expression by siRNA, the interleukin-10-indueced invasion of MKN-45 cells was significantly reduced (10 250±1 500 vs. 2 325±300, P=0.027) and the activation of PI3K/Akt signaling pathway was also suppressed. Furthermore, preincubation of Ly294002 (10 nmol/L), the specific inhibitor of PI3K/Akt signaling pathway, not only prohibit the activation of PI3K/Akt signaling pathway but also obviously diminished interleukin-10-induced invasion of MKN-45 cells (2 050±400 vs. 11 500±1 750, P=0.016). Conclusion Interleukin-10-promoted invasion of MKN-45 gastric cancer cells is mediated by CDH17 through PI3K/Akt signaling pathway. Key words: Interleukin-10; Gastric cancer cells; Cadherin 17; Phosphoinositide-3-kinase signaling; Invasion