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中国临床药理学与治疗学 ›› 2019, Vol. 24 ›› Issue (6): 623-629.doi: 10.12092/j.issn.1009-2501.2019.06.004

• 基础研究 • 上一篇    下一篇

miR-222、MBD2在胃癌患者中的表达及对铂类化疗敏感性的影响

戴 蕾1,罗灵和1,吴黎艳1,王 刚2,费保莹1   

  1. 1浙江省立同德医院消化内科,杭州 310012,浙江;2浙江省立同德医院肿瘤实验室,杭州 310012,浙江
  • 收稿日期:2019-01-31 修回日期:2019-05-14 出版日期:2019-06-26 发布日期:2019-06-25
  • 作者简介:戴蕾,女,硕士,主治医师,主要研究消化系统疾病。 Tel:13588415752 E-mail:alicemouse34@163.com
  • 基金资助:

    浙江省中医药管理局中医药科技计划项目(2018ZA022)

Expression of miR-222 and MBD2 in gastric cancer patients and their effects on platinum chemosensitivity

DAI Lei 1, LUO Linghe 1, WU Liyan 1, WANG Gang 2, FEI Baoying 1   

  1. 1 Department of Gastroenterology, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China; 2 Cancer Laboratory, Tongde Hospital of Zhejiang Province, Hangzhou 310012, Zhejiang, China
  • Received:2019-01-31 Revised:2019-05-14 Online:2019-06-26 Published:2019-06-25

摘要:

目的:研究miRNA-222与甲基化CpG结合结构蛋白2(MBD2)水平在胃癌组织中的表达水平及其对铂类化疗敏感性的影响。方法:选择2016年2月至2017年5月在本院就诊的75例原发性胃癌患者作为研究对象。检测患者癌组织及癌旁组织中miR-222、MBD2表达水平;分析miR-222、MBD2水平与胃癌临床病理参数的相关性。将miR-222 inhibitor转染至胃癌SGC-7901细胞中,RT-PCR和Western blot分别检测转染后细胞中miR-222和MBD2的表达水平,MTT法、流式细胞术分别检测转染对细胞增殖、凋亡的影响。结果:胃癌组织中miR-222的阳性表达率显著高于癌旁组织(P<0.05)。胃癌组织中miR-222相对表达量显著高于癌旁组织(P<0.05)。胃癌组织中MBD2的阳性表达率显著低于癌旁组织(P<0.05)。miR-222及MBD2表达水平与分化程度、TNM分期有明显相关性(P<0.05)。转染miR-222 inhibitor的各组SGC-7901细胞中miR-222表达水平均显著低于空白对照组(Control组)和miR-NC组(NC组)(P<0.05)。转染miR-222 inhibitor的各组细胞中MBD2 mRNA和蛋白表达水平显著高于Control组和NC组(P<0.05)。转染miR-222 inhibitor的各组细胞的增殖率显著低于Control组和NC组(P<0.05),且miR-222 inhibitor+顺铂(Cisplatin,CDDP )组的细胞增殖率显著低于miR-222 inhibitor组及CDDP 组,细胞凋亡率显著高于miR-222 inhibitor组及CDDP 组(P<0.05),且与CDDP联合运用能够更明显地抑制肿瘤细胞的增殖率,促进细胞的凋亡。结论:miR-222在胃癌组织中表达明显上调,MBD2显著下调,其表达高低与胃癌分化程度、TNM分期有明显相关性。miR-222可增强 CDDP 对胃癌的化疗敏感性,其可能通过抑制胃癌中的靶基因MBD2发挥作用。

关键词: 胃癌, miR-222, MBD2, 凋亡

Abstract:

AIM: To study the expression level of miRNA-222 and methylated CpG binding structural protein 2 (MBD2) in gastric cancer and its effect on proliferation and apoptosis of human gastric cancer cells. METHODS:Seventy-five patients with primary gastric cancer who were admitted to our hospital from February 2016 to May 2017 were selected as subjects. The expression levels of miR-222 and MBD2 in cancer tissues and adjacent tissues were detected. The correlation between miR-222 and MBD2 levels and clinicopathological parameters of gastric cancer were analyzed. The miR-222 inhibitor was transfected into gastric cancer SGC-7901 cells. The expression levels of miR-222 and MBD2 were detected by RT-PCR and Western blot, respectively. MTT assay and flow cytometry were used to detect. The effects of transfected cells on proliferation and apoptosis. RESULTS:The positive expression rate of miR-222 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The relative expression of miR-222 in gastric cancer tissues was significantly higher than that in adjacent tissues (P<0.05). The positive expression rate of MBD2 in gastric cancer tissues was significantly lower than that in adjacent tissues (P<0.05). The expression levels of miR-222 and MBD2 were significantly correlated with the degree of differentiation and TNM stage (P<0.05). The expression level of miR-222 in SGC-7901 cells transfected with miR-222 inhibitor was significantly lower than that in control group and NC group (P<0.05). The expression levels of MBD2 mRNA and protein in the cells transfected with miR-222 inhibitor were significantly higher than those in control group and NC group (P<0.05). The proliferation rate of cells transfected with miR-222 inhibitor was significantly lower than that of Control group and NC group (P<0.05), and the cell proliferation rate of miR-222 inhibitor+CDDP group was significantly lower than that of miR-222 inhibitor group and CDDP group. The apoptosis rate was significantly higher than that of miR-222 inhibitor group and CDDP group (P<0.05), and combined with CDDP could inhibit the proliferation rate of tumor cells and promote cell apoptosis. CONCLUSION: The expression of miR-222 in gastric cancer tissues is up-regulated in advanced gastric cancer tissues, and MBD2 is down-regulated significantly. The expression level of miR-222 is significantly correlated with the differentiation degree of gastric cancer and TNM stage. miR-222 can enhance the chemosensitivity of CDDP to gastric cancer,which may play a role in inhibiting the target gene MBD2 in gastric cancer.

Key words: gastric cancer, miR-222, MBD2, apoptosis

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