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《天津医科大学学报》[ISSN:1006-8147/CN:12-1259/R]

卷:

28卷

期数:

2022年03期

页码:

266-271

栏目:

基础医学

出版日期:

2022-05-20

文章信息/Info

Title:

Exogenous IL-6 promotes cisplatin resistance of ovarian cancer through STAT3 pathway

文章编号:

1006-8147(2022)03-0266-06

作者:

沈洋洋¹; 牛秀珑²; 郁春艳¹; 郑小燕¹; 刘俊汝¹; 邓为民¹

（1.天津医科大学基础医学院免疫学系，国家教育部免疫微环境与疾病重点实验室，天津300070；2.中国人民 武装警察部队特色医学中心勤务环境皮肤疾病防治研究所，天津300162）

Author(s):

SHEN Yang-yang¹; NIU Xiu-long²; YU Chun-yan¹; ZHENG Xiao-yan¹; LIU Jun-ru¹; DENG Wei-min¹

（1.Department of Immunology，School of Basic Medical Sciences，Tianjin Medical University，Key Laboratory of Diseases and Microenvironment of Ministry of Education of China，Tianjin 300070，China; 2.Department of Prevention，Therapy of Skin Disease in the Security Environment，Characteristic Medical Center of Chinese People′s Armed Police Force，Tianjin 300162，China）

关键词:

卵巢癌; IL-6; STAT3; 耐药

Keywords:

hovarian cancer;  IL-6;  STAT3;  drug resistance

分类号:

R737.31

DOI:

-

文献标志码:

A

摘要:

目的：探讨外源性白细胞介素-6（IL-6）诱导卵巢癌（OvCa）对顺铂（Cisplatin）耐药的作用。方法：6孔板接种A2780 细胞， 分为对照（Control）组、AG490 组、重组人IL-6（rhIL-6）组和rhIL-6+AG490 组，应用Western 印迹检测rhIL-6 对A2780（顺铂敏 感OvCa 细胞株）的磷酸化信号转导与转录激活因子3（p-STAT3）蛋白表达的影响。96 孔板接种A2780 细胞，分为Control 组、 AG490 组、顺铂（Cisplatin）组、AG490+Cisplatin 组、rhIL-6 组、rhIL-6+AG490 组、rhIL-6+Cisplatin 组和rhIL-6+AG490+Cisplatin 组，CCK8 实验检测rhIL-6 对A2780 细胞增殖的影响。12 孔板接种A2780 细胞， 分为Control 组、AG490 组、Cisplatin 组、 AG490+Cisplatin 组、rhIL-6 组、rhIL-6+AG490 组、rhIL-6+Cisplatin 组和rhIL-6+AG490+Cisplatin 组， 细胞凋亡实验检测rhIL-6 对A2780细胞顺铂耐药的影响。以36 只雌性裸鼠为研究对象，随机分为Control 组、rhIL-6 组、Cisplatin 组、AG490 组、rhIL-6+ Cisplatin 组和rhIL-6+AG490+Cisplatin组， 每组6只。腹腔注射A2780细胞， 给药4 周后颈椎脱臼处死小鼠， 检测rhIL-6 对 OvCa 腹腔种植瘤耐药的影响。结果：Western 印迹结果显示，与Control 组相比，rhIL-6 组p-STAT3 蛋白表达显著增加（t=6.55， P<0.01）；CCK8 实验结果显示，与Control 组相比，rhIL-6 组细胞增殖增加（t=4.148，P<0.05）；细胞凋亡实验发现，与Cisplatin 组 相比，rhIL-6+Cisplatin 组细胞凋亡显著降低（t=20.03，P<0.001），与rhIL-6+Cisplatin 组相比，rhIL-6+Cisplatin+AG490 组细胞凋 亡显著增加（t=22.16，P<0.001）；小鼠体内实验结果发现，与Cisplatin 组相比，rhIL-6+Cisplatin 组瘤结节数量和重量显著增加（t= 2.783，P<0.05），与rhIL-6+Cisplatin组相比，rhIL-6+Cisplatin+AG490 组瘤结节数量和重量显著降低（t=3.306，P<0.05）。结论：外 源性IL-6通过STAT3通路诱导OvCa 对顺铂耐药。

Abstract:

Objective：To investigate the effect of exogenous interleukin-6（IL-6）on cisplatin resistance of ovarian cancer（OvCa）. Methods: A2780 cells were seeded in a 6-well plate，which were divided into Control group，AG490 group，recombinant human IL-6 （rhIL -6）group and rhIL -6 +AG490 group. Western blotting was used to detect the effect of rhIL -6 on the protein expression of phosphorylated signal transduction and activator of transcription 3（p-STAT3）in A2780（cisplatin-sensitive OvCa cell line）. A2780 cells were seeded in a 96-well plate，divided into Control group，AG490 group，Cisplatin group，AG490+Cisplatin group，rhIL-6 group，rhIL-6+ AG490 group，rhIL-6+Cisplatin group and rhIL-6+AG490+Cisplatin group. CCK8 experiment was applied to detect the effect of rhIL-6 on the proliferation of A2780. A2780 cells were seeded in a 12-well plate and divided into Control group，AG490 group，Cisplatin group， AG490+Cisplatin group，rhIL-6 group，rhIL-6+AG490 group，rhIL-6+Cisplatin group and rhIL-6+AG490+Cisplatin group. Apoptosis experiment was used to detect the effect of rhIL-6 on cisplatin resistance of A2780 cells. A total of 36 female nude mice were randomly divided into Control group，rhIL-6 group，Cisplatin group，AG490 group，rhIL-6+Cisplatin group and rhIL-6+AG490+Cisplatin group，with 6 mice in each group. A2780 cells were injected intraperitoneally，and the mice were sacrificed by cervical dislocation four weeks after the administration. The effect of rhIL-6 on the drug resistance of OvCa intraperitoneal implanted tumors was tested. Results: Western blotting results showed that the expression of p-STAT3 protein in the rhIL-6 group was significantly increased compared with the Control group （t=6.55，P<0.01）.The CCK8 experiment results showed that the cell proliferation of the rhIL-6 group was increased compared with the Control group（t=4.148，P<0.05）.Apoptosis experiment found that compared with Cisplatin group，rhIL-6+Cisplatin group cell apoptosis was significantly reduced（t=20.03，P<0.001）.Compared with rhIL-6+Cisplatin group，rhIL-6+Cisplatin+AG490 group cell apoptosis increased significantly（t=22.16，P<0.001）. In vivo experiments in mice found that compared with Cisplatin group，the number and weight of tumor nodules in rhIL-6+Cisplatin group increased significantly（t=2.783，P<0.05）. Compared with the rhIL-6+Cisplatin group，the number and weight of tumor nodules in the rhIL-6+Cisplatin+AG490 group were significantly reduced（t=3.306，P<0.05）. Conclusion: Exogenous IL-6 induces cisplatin resistance in OvCa through STAT3 pathway.

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备注/Memo

备注/Memo:

基金项目天津市自然科学基金重点项目（18YFZCSY00040）；京津冀基础研究合作专项（20JCZXJC00140）；天津市自然科学基金绿色通道 项目（17JCYBJC41200）
作者简介:沈洋洋（1997-），男，硕士在读，研究方向：肿瘤免疫；
通信作者:邓为民，E-mail：dengweimin@tmu.edu.cn。

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更新日期/Last Update: 2022-06-01