ALW-II-41-27, an EphA2 inhibitor, inhibits proliferation, migration and invasion of cervical cancer cells via inhibition of the RhoA/ROCK pathway

Abstract

Recent studies have shown that the Eph receptor A2 (EphA2) and its inhibitor ALW-II-41-27 could regulate various cellular processes in several types of cancer. However, the manner in which ALW-II-41-27 affects the development of cervical cancer (CC) remains unknown. The present study aimed to evaluate the role of ALW-II-41-27 in inhibiting the proliferation, invasion and migration of human papilloma virus-positive CC cells and to verify whether Ras homolog family member A (RhoA)/Rho-associated protein kinase (ROCK) may be a crucial pathway involved in this process. Reverse transcription-quantitative PCR and western blotting analyses indicated an upregulation of EphA2 expression in CC cell lines (HeLa and CaSki). Furthermore, the results from MTT and colony formation assays indicated that ALW-II-41-27 inhibited cell proliferation. Results from wound healing and Transwell assays further demonstrated the inhibitory effect of ALW-II-41-27 on CaSki and HeLa cell migration and invasion, respectively. Furthermore, ALW-II-41-27 inhibited the protein expression of GTP-RhoA and ROCK1 in CaSki and HeLa cells. In addition, the ALW-II-41-27-induced inhibition of the biological function of CaSki and HeLa cells was promoted by cell co-culture with RhoA and ROCK inhibitors. Taken together, the present findings revealed that ALW-II-41-27 inhibited CC cell proliferation, migration and invasion by blocking the RhoA/ROCK pathway. These findings provide further insight into the mechanism of CC progression and significant information for the development of potential therapeutic targets for CC.