miR-95与胃癌细胞洛铂敏感性的关系及作用机制研究

doi:10.3969/j.issn.1004-616x.2019.05.005

癌变·畸变·突变 ›› 2019, Vol. 31 ›› Issue (5): 363-367,372.doi: 10.3969/j.issn.1004-616x.2019.05.005

miR-95与胃癌细胞洛铂敏感性的关系及作用机制研究

温转¹, 檀碧波², 李勇², 赵群², 范立侨², 王冬², 尔丽绵³

1. 河北医科大学第四医院质量控制办公室, 河北石家庄 050011;
2. 河北医科大学第四医院外三科, 河北石家庄 050011;
3. 河北医科大学第四医院内镜室, 河北石家庄 050011

收稿日期:2019-04-10 修回日期:2019-07-30 出版日期:2019-09-30 发布日期:2019-10-09
通讯作者: 李勇,E-mail:li_yong_hbth@126.com E-mail:li_yong_hbth@126.com
作者简介:温转,E-mail:jiayouwenzhuan@163.com。
基金资助:
河北省医学科学研究重点课题计划项目（20170145）

Expression of miR-95 and susceptibility to lobaplatin in gastric cancer cells

WEN Zhuan¹, TAN Bibo², LI Yong², ZHAO Qun², FAN Liqiao², WANG Dong², ER Limian³

1. Quality Control Office, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011;
2. Third Department of Surgery, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011;
3. Endoscopy Department, the Fourth Hospital of Hebei Medical University, Shijiazhuang 050011, Hebei, China

Received:2019-04-10 Revised:2019-07-30 Online:2019-09-30 Published:2019-10-09

摘要/Abstract

摘要： 目的：探讨miR-95与胃癌细胞洛铂敏感性的关系及作用机制。方法：收集30例手术切除的胃癌组织及癌旁组织标本，实时定量PCR（qPCR）法检测组织中miR-95的表达情况，CCK-8法检测洛铂对胃癌组织细胞的体外抑制率。采用miR-95抑制物（anti-miR-95）和miR-95模拟物（miR-95 mimics）分别转染人胃癌细胞株SGC7901，检测转染前后细胞对洛铂敏感性的变化；采用qPCR及Western blot法检测细胞耐药相关基因MDR1、GST-π、LRP、Survivin、xIAP、Bad mRNA和蛋白的表达。结果：qPCR检测结果显示，30例胃癌组织miR-95的相对表达水平（0.106±0.023）显著高于癌旁组织（0.046±0.025）（P < 0.05）。以miR-95表达均值为界将胃癌组织分为miR-95高表达组17例，低表达组13例。洛铂对miR-95表达水平高的胃癌细胞的抑制率低于miR-95低水平者（P < 0.05）。anti-miR-95转染后，SGC7901细胞对洛铂的敏感性明显增高（P < 0.01），耐药相关基因MDR1、Survivin、xIAP mRNA和蛋白表达水平明显降低（P < 0.05），而Bad mRNA和蛋白表达水平明显增高（P < 0.05）。miR-95 mimics转染后，洛铂对SGC7901细胞的抑制率明显增加（P < 0.01），耐药相关基因MDR1、Survivin、xIAP mRNA和蛋白表达水平明显升高（P < 0.05），而Bad mRNA和蛋白表达水平明显降低（P < 0.05）。结论：miR-95通过调节一些耐药基因的表达影响胃癌组织和细胞对洛铂的敏感性。

关键词: 微小RNA-95, 胃癌, 洛铂, 药物敏感性

Abstract: OBJECTIVE:To investigate the relationship between microRNA-95 (miR-95) expression and chemoresistance of gastric cancer cells to lobaplatin. METHODS:Expression of miR-95 in the cancer and paracancerous tissues from 30 patients with gastric cancer was detected using real time PCR. CCK-8 was used to detect sensitivity of gastric cancer tissues to lobaplatin in vitro. Anti-miR-95 and miR-95 mimics were transfected into SGC7901 to determine changes in inhibition rates of lobaplatin. Real-time quantitative PCR and Western blot were used to detect expression of the multidrug resistant genes:MDR1,GST-π,LRP,Survivin,xIAP and Bad. RESULTS:Levels of miR-95 in gastric cancers were higher than that in paracancerous tissues (P < 0.05). The cancer tissues with higher miR-95 expression levels showed higher activities after lobaplatin treatment (P < 0.05). After transfection with anti-miR-95 cells,sensitivity to lobaplatin increased significantly (P < 0.01). The mRNA and protein expressions of MDR1,Survivin and xIAP decreased significantly after the transfection (P < 0.05),while the expression of Bad mRNA and protein increased significantly (P < 0.05). After the transfection with miR-95 mimics,sensitivity of cells to lobaplatin decreased significantly (P < 0.01). The mRNA and protein expressions of MDR1,Survivin and xIAP significantly after the transfection (P < 0.05),while the expression of Bad mRNA and protein decreased significantly(P < 0.05). CONCLUSION:miR-95 was involved with sensitivity of gastric cancer cells to lobaplatin via regulation of some resistance-related genes.

Key words: microRNA-95, gastric cancer, lobaplatin, drug sensitivity

中图分类号:

R735.2

温转, 檀碧波, 李勇, 赵群, 范立侨, 王冬, 尔丽绵. miR-95与胃癌细胞洛铂敏感性的关系及作用机制研究[J]. 癌变·畸变·突变, 2019, 31(5): 363-367,372.

WEN Zhuan, TAN Bibo, LI Yong, ZHAO Qun, FAN Liqiao, WANG Dong, ER Limian. Expression of miR-95 and susceptibility to lobaplatin in gastric cancer cells[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2019, 31(5): 363-367,372.

参考文献

[1] CHEN W Q, ZHENG R, BAADE P D, et al. Cancer statistics in China, 2015[J]. CA Cancer J Clin, 2016, 66(2):115-132. doi:10.3322/caac.21338.
[2] DUAN S Q, YIN J, BAI Z G, et al. Effects of taxol resistance gene 1 on the cisplatin response in gastric cancer[J]. Oncol Lett, 2018, 15(6):8287-8294.
[3] ZHOU L, LI X W, ZHOU F, et al. Downregulation of leucine-rich repeats and immunoglobulin-Like domains 1 by microRNA-20a modulates gastric cancer multidrug resistance[J]. Cancer Sci, 2018, 109(4):1044-1054.
[4] FAN B, JIAO B H, FAN F S, et al. Downregulation of miR-95-3p inhibits proliferation, and invasion promoting apoptosis of glioma cells by targeting CELF2[J]. Int J Oncol, 2015, 47(3):1025-1033.
[5] CHEN X C, CHEN S M, HANG W J, et al. MiR-95 induces proliferation and chemo-or radioresistance through directly targeting sorting nexin1(SNX1) in non-small cell lung cancer[J]. Biomedecine Pharmacother, 2014, 68(5):589-595.
[6] QIN J, TENG J A, ZHU Z, et al. Glargine promotes human colorectal cancer cell proliferation via upregulation of miR-95[J]. Horm Et Metab, 2015, 47(11):861-865.
[7] ZHANG Y L, YANG Q, WANG S W. MicroRNAs:a new key in lung cancer[J]. Cancer Chemother Pharmacol, 2014, 74(6):1105-1111.
[8] HUA S H, KONG X Y, CHEN B B, et al. Anticancer mechanism of lobaplatin as monotherapy and in combination with paclitaxel in human gastric cancer[J]. Curr Mol Pharmacol, 2018, 11(4):316-325.
[9] PATTISON S, MITCHELL C, LADE S, et al. Early relapses after adjuvant chemotherapy suggests primary chemoresistance in diffuse gastric cancer[J]. PLoS One, 2017, 12(9):e0183891. DOI:10.1371/journal.pone.0183891.
[10] 李勇, 檀碧波. 胃癌耐药的研究现状及趋势[J]. 世界华人消化杂志, 2016, 24(32):4330-4336.
[11] CHEN T, WANG C Y, LIU Q, et al. Dasatinib reverses the multidrug resistance of breast cancer MCF-7 cells to doxorubicin by downregulating P-gp expression via inhibiting the activation of ERK signaling pathway[J]. Cancer Biol Ther, 2015, 16(1):106-114.
[12] YANG L L, DU C J, WU L, et al. Cytokine-induced killer cells modulates resistance to cisplatin in the A549/DDP cell line[J]. J Cancer, 2017, 8(16):3287-3295.
[13] 李勇, 檀碧波, 赵群, 等. 抑制miR-185对人胃癌细胞株SGC7901药物敏感性影响的机制探讨[J]. 中华肿瘤防治杂志, 2015, 22(17):1347-1351.
[14] PLAAT B E, MOLENAAR W M, SAGRUDNY J, et al. The 16p11 breakpoint in myxoid liposarcomas might affect the expression of the LRP gene on 16p11.2 encoding the multidrug resistance associated major vault protein[J]. Eur J Clin Invest, 2000, 30(5):447-453.
[15] TANAKA T, UCHIDA H. Inhibition of survivin by adenovirus vector enhanced paclitaxel-induced apoptosis in breast cancer cells[J]. Anticancer Res, 2018, 38(7):4281-4288.
[16] MIYAMOTO M, TAKANO M, AOYAMA T, et al. Phenoxodiol increases cisplatin sensitivity in ovarian clear cancer cells through XIAP down-regulation and autophagy inhibition[J]. Anticancer Res, 2018, 38(1):301-306.
[17] XI M, CHENG L, HUA W, et al. MicroRNA-95-3p promoted the development of prostatic cancer via regulating DKK3 and activating Wnt/β-catenin pathway[J]. Eur Rev Med Pharmacol Sci, 2019, 23(3):1002-1011.
[18] YE J, YAO Y F, SONG Q X, et al. Up-regulation of miR-95-3p in hepatocellular carcinoma promotes tumorigenesis by targeting p21 expression[J]. Sci Rep, 2016, 6:34034.

miR-95与胃癌细胞洛铂敏感性的关系及作用机制研究

Expression of miR-95 and susceptibility to lobaplatin in gastric cancer cells

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