中国癌症杂志 ›› 2020, Vol. 30 ›› Issue (11): 858-864.doi: 10.19401/j.cnki.1007-3639.2020.11.002

• 论著 • 上一篇    下一篇

miR-503靶向TLR4对前列腺癌多西他赛耐药的影响

周 舰,张朝阳,孙 伟,杨 军,张志超,戚晓红   

  1. 武汉市第三医院泌尿外科,湖北 武汉 430060
  • 出版日期:2020-11-30 发布日期:2020-12-04
  • 通信作者: 周 舰 E-mail: tancan73012@126.com
  • 基金资助:
    2019武汉市卫生健康委科研项目(WX19D67)。

Effects of miR-503 targeting TLR4 on drug resistance to docetaxel in prostate cancer

ZHOU Jian, ZHANG Chaoyang, SUN Wei, YANG Jun, ZHANG Zhichao, QI Xiaohong   

  1. Department of Urology, Wuhan Third Hospital, Wuhan 430060, Hubei Province, China
  • Published:2020-11-30 Online:2020-12-04
  • Contact: ZHOU Jian E-mail: tancan73012@126.com

摘要: 背景与目的:在前列腺癌标准化疗方案中,多西他赛(docetaxel,DTX)引起的化疗耐药是引起患者死亡的重要原因之一,然而DTX引起的化疗耐药相关机制尚未知。探讨前列腺癌DTX耐药的作用机制。方法:收集2016年6月—2019年6月在武汉市第三医院进行化疗的40例患者,包括20例DTX耐药和20例DTX敏感患者。人前列腺癌细胞系PC-3在一系列逐渐增加的DTX浓度梯度处理下形成耐药株PC-3/DTX。采用实时荧光定量聚合酶链反应(real-time fluorescence quantitative polymerase chain reaction,RTFQ-PCR)检测miR-503和TLR4 mRNA的表达,采用蛋白质印迹法(Western blot)检测TLR4蛋白的水平,采用双荧光素酶报告基因检测miR-503和TLR4的相互作用,采用四甲基偶氮唑蓝(methyl thiazolyl tetrazolium,MTT)法检测细胞活力,采用流式细胞术检测细胞凋亡。结果:前列腺癌耐药患者组织和耐药细胞系中miR-503的表达较敏感组显著降低(P=0.013),而TLR4显著增加(P=0.005 6)。过表达miR-503显著抑制耐药细胞的增殖,促进凋亡,同时抑制耐药相关蛋白MDR-1的表达,而过表达TLR4则促进细胞的增殖,抑制凋亡,促进耐药相关蛋白MDR-1的表达。结论:miR-503通过靶向调控TLR4的表达影响前列腺癌的DTX耐药。

关键词: 前列腺癌, miR-503, TLR4, 多西紫杉醇, 耐药

Abstract: Background and purpose: In the standard chemotherapy for prostate cancer, docetaxel (DTX) resistance is one of the important causes of death in patients. However, the potential mechanism of DTX chemoresistance is still unclear. Therefore, this study aimed to explore the potential mechanism of DTX resistance in prostate cancer. Methods: A total of 40 patients with prostate cancer who received chemotherapy in the Wuhan Third hospital, including 20 patients with resistance and 20 patients with sensitivity to DTX, were enrolled, and the tumor tissues were collected during surgery. The resistant cells PC-3/DTX were PC-3 cells induced by DTX. Real-time fluorescence quantitative polymerase chain reaction (RTFQ-PCR) was performed to detect the mRNA expressions of miR-503 and TLR4. Western blot was conducted to detect TLR4 protein expression. The interaction between miR-503 and TLR4 was determined by luciferase reporter assay. Cell viability and apoptosis were determined by methyl thiazolyl tetrazolium (MTT) assay and flow cytometry, respectively. Results: The expression of miR-503 was decreased (P=0.013), while TLR4 was increased in the resistant tissues and cells (P=0.005 6). Overexpression of miR-503 suppressed cell viability, induced cell apoptosis, and inhibited expression of drug resistance-related protein MDR-1. Furthermore, overexpression of TLR4 reversed the effects of miR-503 overexpression. Conclusion: miR-503 targets TLR4 to regulate its expression, and affects resistance to DTX in prostate cancer.

Key words: Prostate cancer, miR-503, TLR4, Docetaxel, Resistance