...
  • 主题
高级搜索  >
历史搜索 清空历史
首页> 外文期刊>Cell Division >Overexpression of P16 reversed the MDR1-mediated DDP resistance in the cervical adenocarcinoma by activating the ERK1/2 signaling pathway
【24h】

Overexpression of P16 reversed the MDR1-mediated DDP resistance in the cervical adenocarcinoma by activating the ERK1/2 signaling pathway

机译：P16的过度表达通过激活ERK1 / 2信号通路逆转了MDR1介导的宫颈腺癌中DDP耐药性。

获取原文
           
页面导航
  • 摘要
  • 著录项
  • 相似文献
  • 相关主题

摘要

To investigate the role of P16 (INK4a)-extracellular signal related kinase 1/2 (ERK1/2) signaling pathway in cisplatin (DDP) resistance induced by multidrug resistance protein 1 (MDR1), also known as P-glycoprotein (P-gp), in cervical adenocarcinoma. A human DDP-resistant HeLa cell line (HeLa/DDP) was constructed using the combination of incremental and intermittent administration of DDP. Cell Counting Kit-8 (CCK-8) assay was used to measure the IC50 and resistance index (RI) of cells. The morphological changes and population doubling time were observed under an inverted microscope. Plate cloning formation assay was performed to evaluate the cell proliferation and tumorigenic ability. Cell invasion and migration were determined by transwell assays. Besides, the expression of P16, phosphorylated extracellular signal related kinase 1 and 2 (pERK1/2), total ERK1/2 and MDR1 were measured using western blot analysis.?The ERK-specific inhibitor U0126 and agonist TPA was used to explore the role of ERK. The DDP-resistant cervical adenocarcinoma HeLa/DDP cell line was successfully established, which showed stronger cell growth, invasion, and migration. In the HeLa/DDP cells, pERK1/2 was downregulated,?P-gp was upregulated?and P16 was downregulated. Overexpression of P16 led to a significant decrease in the proliferation rate, migration ability, and invasion ability of the HeLa/DDP cells. Furthermore, overexpression of P16 increased and the decreased expression of pERK1/2 and P-gp in the HeLa/DDP cells, respectively. Treatment of HeLa/DDP cells transfected with P16 plasmid with ERK-specific inhibitor U0126 significantly decreased the expression of pERK1/2?and increased the expression of P-gp from 6 h to 48 h. Moreover, after 72 h, the expression of pERK1/2 was up-regulated and the expression of P-gp was inhibited. Overexpression of P16 could partially reverse the MDR1-mediated DDP resistance in the cervical adenocarcinoma by the enhancement of phosphorylation of ERK signaling pathway, which provided a theoretical basis for the treatment of DDP resistance in cervical adenocarcinoma.
机译：研究P16（INK4a）-细胞外信号相关激酶1/2（ERK1 / 2）信号通路在多药耐药蛋白1（MDR1），也称为P-糖蛋白（P-gp）诱导的顺铂（DDP）耐药中的作用），宫颈腺癌。使用DDP增量和间歇给药的组合构建了抗人DDP的HeLa细胞系（HeLa / DDP）。使用Cell Counting Kit-8（CCK-8）分析法测量细胞的IC50和抗性指数（RI）。倒置显微镜下观察形态变化和种群倍增时间。进行平板克隆形成测定以评估细胞增殖和致瘤能力。细胞侵袭和迁移通过transwell测定法确定。此外，采用蛋白质印迹法检测P16，磷酸化细胞外信号相关激酶1和2（pERK1 / 2），总ERK1 / 2和MDR1的表达。采用ERK特异性抑制剂U0126和激动剂TPA探讨其作用。 ERK。成功建立了对DDP耐药的宫颈腺癌HeLa / DDP细胞系，显示出更强的细胞生长，侵袭和迁移能力。在HeLa / DDP细胞中，pERK1 / 2被下调，p-gp被上调，P16被下调。 P16的过度表达导致HeLa / DDP细胞的增殖速率，迁移能力和侵袭能力显着降低。此外，在HeLa / DDP细胞中，P16的过表达分别增加而pERK1 / 2和P-gp的表达减少。用ERK特异性抑制剂U0126处理转染了P16质粒的HeLa / DDP细胞，从6 h到48 h显着降低pERK1 /2β的表达，并增加P-gp的表达。此外，在72小时后，pERK1 / 2的表达被上调并且P-gp的表达被抑制。 P16的过表达可以通过增强ERK信号通路的磷酸化来部分逆转MDR1介导的宫颈腺癌DDP耐药性，为宫颈腺癌DDP耐药性的治疗提供理论依据。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱：kefu@zhangqiaokeyan.com

京公网安备：11010802029741号 ICP备案号：京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有

  • 客服微信

  • 服务号