Rho-associated protein kinase inhibitor Y-27632 increases the sensitivity of lung adenocarcinoma A 549 cells to matrine via the Rad 51 / ERCC 1 signaling pathway

Purpose: Non-small cell lung carcinoma (NSCLC) is one of the most lethal types of cancer. The aim of this study was to investigate the potential of Y-27632, which is a selective inhibitor of ROCK/Rho-kinase, to enhance the antitumor effects of matrine, a major alkaloid component extracted from the traditional Chinese herb Sophora flavescens Ait, on lung adenocarcinoma A549 cells. Methods: A549 cells were treated with different concentrations of matrine alone or in combination with Y-27632 for 48 h and cell viability, migration, and apoptosis were assessed. The mRNA and protein levels of the DNA repair-related molecules Rad51 and ERCC1 were determined by qRT-PCR and Western blot analysis, respectively. Results: Matrine inhibited A549 cell viability in a doseand time-dependent manner. However, when A549 cells were treated with matrine combined with Y-27632, the decreases in cell viability and migration were greater than those observed following treatment with matrine alone. Matrine in combination with Y-27632 induced apoptosis more effectively than matrine alone. Notably, the mRNA and protein levels of Rad51 and ERCC1 were also suppressed by treatment with the combination of matrine and Y-27632. Conclusion: Y-27632 increases the sensitivity of A549 cells to matrine in regulating cell proliferation, migration and apoptosis. The effect of the combination of matrine and Y-27632 on A549 cells is likely to be related to Rad51/ERCC1 signaling.