Asiatic acid enhances the chemosensitivity of U87MG glioma cells to paclitaxel through inhibiting the expression of drug resistance related proteins / 中国肿瘤生物治疗杂志

ABSTRACT

@#[Abstract] Objective: To explore the inhibitive effect of asiatic acid (AA) on paclitaxel (PTX)-resistant glioma cells and its possible mechanism. Methods: The effects of AA on the proliferation and apoptosis of glioblastoma U87MG cells were detected by CCK-8 assay, Real-time quantitative polymerase chain reaction (qPCR) and Western blotting. The drug-resistant glioma cell line PR-U87MG was established by culturing the cells in concentration-increasing PTX. With U87MG cells as control, the PTX-resistance of PR-U87MG cells was confirmed using CCK-8 assay, and the mRNA and protein levels of MDR1 and LRP were measured with qPCR and western blotting. PR-U87MG cells were treated with AA, PTX or AA+PTX, and then the cell viability and apoptosis of each group were measured with CCK-8 assay, qPCR and Western blotting. Results: PTX-resistant PR-U87MG cell line was successfully established. AA inhibited the viability of U87MG and PR-U87MG cells in a dose-dependent manner (P<0.01) and significantly promoted their apoptosis (P<0.01). Compared with the group treated with AA or PTX alone, the group treated with the combination of AA and PTX had significantly decreased protein levels of PARP1 (P<0.01), drug-resistant related proteins (Pgp-1 and LRP [lung resistance protein], all P< 0.01), and markedly increased caspase 3 (P<0.01). Conclusion: AA could effectively enhance the sensitivity of U87MG cells to PTX, and the mechanism may be related to the suppressed expression of drug efflux-associated proteins Pgp-1 and LRP.