摘要
目的 基于Hippo-Yes相关蛋白(YAP)信号通路探讨藁本内酯对宫颈癌细胞化疗耐药性的影响.方法 将人宫颈癌顺铂耐药细胞HeLa/DDP分为对照组、顺铂组(10 μmol/L顺铂)和顺铂+低、中、高浓度藁本内酯组(10 μmol/L顺铂+25、50、100 μmol/L藁本内酯),检测各组细胞的增殖、凋亡、迁移、侵袭情况,以及YAP、具有PDZ结合基序的转录共激活因子(TAZ)mRNA和YAP、TAZ、基质金属蛋白酶2(MMP2)、Ki67、切割型胱天蛋白酶3(cleaved-caspase-3)、caspase-3蛋白的表达情况.结果 与对照组比较,顺铂组细胞的增殖抑制率、凋亡率和cleaved-caspase-3/caspase-3均显著升高;划痕愈合率、侵袭细胞数,YAP、TAZ mRNA和YAP、TAZ、MMP2、Ki67蛋白的表达水平均显著降低(P＜0.05).与顺铂组比较,顺铂+低、中、高浓度藁本内酯组细胞的增殖抑制率、凋亡率和cleaved-caspase-3/caspase-3均进一步升高;划痕愈合率、侵袭细胞数,YAP、TAZ mRNA和YAP、TAZ、MMP2、Ki67蛋白的表达水平均进一步降低,且呈剂量依赖性(P＜0.05).结论 藁本内酯可通过抑制Hippo-YAP信号通路提高宫颈癌耐药细胞对顺铂的敏感性.
Abstract
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.
国家科技期刊平台
NSTL
万方数据