藁本内酯对宫颈癌细胞化疗耐药性的影响
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篇名: | 藁本内酯对宫颈癌细胞化疗耐药性的影响 |
TITLE: | Effects of ligustilide on chemotherapy resistance of cervical cancer cells |
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(10μmol/L顺铂)和顺铂+低、中、高浓度藁本内酯组(10μmol/L顺铂+25、50、100μmol/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、TAZmRNA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、TAZmRNA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. |
期刊: | 2024年第35卷第13期 |
作者: | 张文渊;王倩;张丽红;周海燕;张妮 |
AUTHORS: | ZHANG Wenyuan,WANG Qian,ZHANG Lihong,ZHOU Haiyan,ZHANG Ni |
关键字: | 藁本内酯;宫颈癌细胞;顺铂;化疗耐药性;Hippo-YAP信号通路 |
KEYWORDS: | ligustilide; cervical cancer cells; cisplatin; chemotherapy resistance; Hippo-YAP signaling pathway |
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