藁本内酯对宫颈癌细胞化疗耐药性的影响OA北大核心CSTPCD

OBJECTIVE To investigate the effects of ligustilide on chemotherapy resistance of cervical cancer cells based on Hippo-Yes-associated protein(YAP)signaling pathway.METHODS Human cervical cancer cisplatin-resistant cells HeLa/DDP were divided into control group,cisplatin group(10 μmol/L cisplatin),cisplatin+ligustilide low-,medium-and high-concentration groups(10 μmol/L cisplatin+25,50,100 μmol/L ligustilide).The proliferation,apoptosis,migration and invasion of HeLa/DDP cells were all detected in each group.The mRNA expressions of YAP and transcriptional coactivator with PDZ binding motif(TAZ)as well as the protein expressions of YAP,TAZ,matrix metalloproteinase 2(MMP2),Ki67,cleaved-caspase-3 and caspase-3 were determined in HeLa/DDP cells.RESULTS Compared with control group,the inhibitory rate,apoptotic rate and cleaved-caspase-3/caspase-3 of cisplatin group were increased significantly;scratch healing rate,the number of invasive cells,the mRNA expressions of YAP and TAZ,and the protein expressions of YAP,TAZ,MMP2 and Ki67 were decreased significantly in cisplatin group(P＜0.05).Compared with cisplatin group,the inhibitory rate of cell proliferation,apoptotic rate and cleaved-caspase-3/caspase-3 were further increased in cisplatin+ligustilide low-,medium-and high-concentration groups,while scratch healing rate,the number of invasive cells,the mRNA expressions of YAP and TAZ,and the protein expressions of YAP,TAZ,MMP2 and Ki67 were further decreased,in a dose-dependent manner(P＜0.05).CONCLUSIONS Ligustilide can increase the sensitivity of drug-resistant cervical cancer cells to cisplatin by inhibiting Hippo-YAP signaling pathway.