中国妇产科临床杂志2024,Vol.25Issue(5) :404-407.DOI:10.13390/j.issn.1672-1861.2024.05.006

MiR-449c-5p对卵巢癌细胞紫杉醇敏感性的影响及机制研究

Effect of MiR-449c-5p on the sensitivity of ovarian cancer cells to paclitaxel and its mechanism

高玉霞 王文翔 李章欢 刘宇 李力 何乾 韩琛
中国妇产科临床杂志2024,Vol.25Issue(5) :404-407.DOI:10.13390/j.issn.1672-1861.2024.05.006

MiR-449c-5p对卵巢癌细胞紫杉醇敏感性的影响及机制研究

Effect of MiR-449c-5p on the sensitivity of ovarian cancer cells to paclitaxel and its mechanism

高玉霞 1王文翔 1李章欢 1刘宇 2李力 1何乾 1韩琛1
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作者信息

  • 1. 新乡市中心医院,新乡医学院第四临床学院妇瘤科,河南新乡 453000
  • 2. 新乡市中心医院,新乡医学院第四临床学院产科,河南新乡 453000
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摘要

目的 探究miR-449c-5p对卵巢癌细胞紫杉醇(paclitaxel,PTX)耐药影响及潜在调控机制.方法 qRT-PCR检测miR-449c-5p表达,蛋白免疫印迹分析ABCC1的蛋白表达.将miR-449c-5p、miR-NC、ABCC1过表达载体以及pcDNA 3.1(+)载体转染PTX耐药的卵巢癌细胞A2780/PTX和SKOV3/PTX,利用CCK-8法以及transwell实验分析细胞表型变化.双荧光素酶报告实验鉴定miR-449c-5p和ABCC1之间的联系.移植瘤鼠模型实验体内分析miR-449c-5p和PTX联合处理对肿瘤生长的影响.结果 与HOSEPiC细胞相比,miR-449c-5p表达在 A2780 和 SKOV3 细胞中较低(P<0.05),在 A2780/PTX 和 SKOV3/PTX 细胞中最低(P<0.05).miR-449c-5p在A2780/PTX和SKOV3/PTX细胞中靶向ABCC1.与miR-NC转染组相比,miR-449c-5p转染组中IC50值降低、侵袭细胞数减少(P<0.05);和miR-449c-5p和pcDNA共转染组比较,miR-449c-5p和ABCC1共转染组的PTX的IC50值显著增加、侵袭细胞数增加(P<0.05).和miR-NC+PBS组比较,鼠模型移植瘤体积在miR-NC+PTX组和miR-449c-5p+PBS组显著降低(P<0.05),与miR-NC+PTX组比较,移植瘤体积在miR-449c-5p+PTX组显著降低(P<0.05).结论 MiR-449c-5p通过调控ABCC1提高卵巢癌对PTX的敏感性.

Abstract

Objective To explore the effects of miR-449c-5p on the paclitaxel(PTX)sensitivity of PTX-resistant ovarian cancer cells and the potential regulatory mechanism.Methods MiR-449c-5p expression was analyzed by qRT-PCR,and ABCC1 protein expression was detected by western blotting assay.PTX-resistant ovarian cancer cells including A2780/PTX and SKOV3/PTX were transfected with miR-449c-5p,miR-NC,ABCC1 overexpression vector and pcDNA 3.1(+)vector,and then cell phenotypic changes were analyzed by CCK-8 assay and transwell assay.Dual-luciferase reporter assay was used to identify the association between miR-449c-5p and ABCC1.The effect of combination treatment of miR-449c-5p and PTX on tumor growth was analyzed in vivo by a xenograft mouse model assay.Results Compared with HOSEPiC cells,miR-449c-5p expression was lower in A2780 and SKOV3 cells(P<0.05),and was the lowest in A2780/PTX and SKOV3/PTX cells(P<0.05).MiR-449c-5p interacted with ABCC1 in A2780/PTX and SKOV3/PTX cells.Compared with the miR-NC transfection group,the miR-449c-5p transfection group showed reduced IC50 value of PTX and the decreased number of invasive cells(P<0.05).Compared with the miR-449c-5p and pcDNA co-transfection group,the IC50 value of PTX and the number of invasive cells in the miR-449c-5p and ABCC1 co-transfection group was significantly increased(P<0.05).Compared with the miR-NC+PBS group,the transplanted tumor volume in the mouse model were significantly decreased in the miR-NC+PTX group and the miR-449c-5p+PBS group(P<0.05),and compared with the miR-NC+PTX group,the transplanted tumor volume was significantly decreased in the miR-449c-5p+PTX group(P<0.05).Conclusion MiR-449c-5p enhanced the sensitivity of ovarian cancer to PTX by interacting with ABCC1.

关键词

卵巢癌/紫杉醇/miR-449c-5p/ABCC1

Key words

ovarian cancer/paclitaxel/miR-449c-5p/ABCC1

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基金项目

河南省医学科技攻关计划联合共建项目(LHGJ20210914)

新乡市科技攻关项目(GG2020041)

出版年

2024
中国妇产科临床杂志
北京大学

中国妇产科临床杂志

CSTPCD北大核心
影响因子:1.095
ISSN:1672-1861
参考文献量2
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