解剖学报

解剖学报 ›› 2020, Vol. 51 ›› Issue (2): 216-219.doi: 10.16098/j.issn.0529-1356.2020.02.011

• 肿瘤生物学 • 上一篇    下一篇

白细胞介素-6对胰腺癌荷瘤小鼠移植瘤生长及Caspase-3/Bax/Bcl-2信号通路的影响

马永超1 杜晓鹃2 李海龙3 崔凤侠2*   

  1. 1.漯河医学高等专科学校 河南省肿瘤发生与防治创新型科技团队， 河南 漯河 462002； 2.承德医学院中药学系， 河北 承德 067000； 3.宁夏回族自治区第三人民医院内科， 银川 750021
  • 收稿日期:2019-01-07 修回日期:2019-05-21 出版日期:2020-04-06 发布日期:2020-04-06
  • 通讯作者: 崔凤侠 E-mail:13839527381@163.com
  • 基金资助:
    IL-6/STAT3/Notch信号通路在慢性胰腺炎恶性转化中的作用及机制;慢性胰腺炎恶性转化分子标记物筛选及机制探讨

Tumorigenic effect of interleukin-6 on mice with pancreatic carcinoma via regulating the Caspase-3/Bax/Bcl-2 signaling pathway#br#

MA Yong-chao1 DU Xiao-juan2 LI Hai-long3 CUI Feng-xia2*   

  1. 1. Luohe Medical College, Tumor Occurrence and Prevention Research Innovation Team of He’nan, He’nan Luohe 462002, China; 2. Department of Traditional Chinese Medicine, Chengde Medical University, Hebei Chengde 067000, China; 3. Department of Internal Medicine, the Third People’s Hospital of Ningxia, Yinchuan 750021, China
  • Received:2019-01-07 Revised:2019-05-21 Online:2020-04-06 Published:2020-04-06
  • Contact: CUI Feng-xia E-mail:13839527381@163.com

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摘要：

目的  探讨白细胞介素（IL)-6促进胰腺癌MPC-83细胞荷瘤小鼠移植瘤生长的Caspase-3/Bax/Bcl-2凋亡信号通路的作用机制。 
 方法  取40只小鼠，腋部皮下注射小鼠胰腺癌MPC-83细胞制作胰腺癌荷瘤动物模型，随机分为空白对照组（A组），腹腔注射PBS 10 ml/kg；IL-6组（B组），腹腔注射重组小鼠IL-6 200 μg/kg；IL-6受体阻断剂组（C组），腹腔注射托珠单克隆抗体100 mg/kg；IL-6+IL-6受体阻断剂组（D组），腹腔注射托珠单抗 100 mg/kg，30 min后再注射重组小鼠IL-6 200 μg/kg，每组10只。各组小鼠每3 d给药1次，持续至28 d。于实验开始后第0、7、14、21及28天，记录瘤体积变化；采用ELISA法检测瘤组织生存素（survivin）和细胞色素C（Cyt-C）含量；采用反转录聚合酶链反应（RT-PCR）和Western blotting法检测瘤组织Caspase-3、Bax及Bcl-2 mRNA和蛋白表达水平。  结果  与A组比较，B组荷瘤小鼠瘤组织第7、14、21及28天生长较快，瘤组织生存素含量升高，细胞色素C含量下降，Caspase-3和Bax mRNA和蛋白表达水平下调，Bcl-2 mRNA和蛋白表达水平上调（P<0.05，P<0.01）；与B组比较，C组与D组荷瘤小鼠瘤组织第14、21及28天生长缓慢，瘤组织生存素含量降低，细胞色素C含量升高，Caspase-3、Bax mRNA和蛋白表达水平升高，Bcl-2 mRNA和蛋白表达水平降低（P<0.05，P<0.01）；C组与D组比较，各检测指标差异无显著性（P> 0.05）。  结论  IL-6促进胰腺癌生长增殖的作用与其调控Caspase-3/Bax/Bcl-2细胞凋亡信号通路相关。

关键词: 白细胞介素-6, 胰腺癌, MPC-83细胞, 反转录聚合酶链反应, 免疫印迹法, 小鼠

Abstract:

Objective  To explore the tumorigenic effect of interleukin(IL)-6 on mice with pancreatic carcinoma and the Caspase-3/Bax/Bcl-2 signaling pathway related mechanism.   Methods  Forty mice were used to establish tumor-bearing animal model of pancreatic cancer with mouse pancreatic cancer cell line MPC-83. The tumor-bearing mice were divided into blank control group (A), intraperitoneal injection PBS 10 ml/kg; IL-6 group (B), intraperitoneal injection recombinant mouse IL-6 200 μg/kg; IL-6 receptor blocker group (C), intraperitoneal injection tocilizumab 100 mg/kg; and IL-6+IL-6 receptor blocker group (D), intraperitoneal injection tocilizumab 100 mg/kg, 30 minutes later, intraperitoneal injection recombinant mouse IL-6 200 μg/kg, 10 mice in each group. The mice in each group were administrated corresponding drug once every 3 days for 28 days. The tumor volume was to observe and record at day 0, 7, 14, 21 and 28 after the experiment began. The mice were sacrificed by cervical vertebra dislocation after the last measurement of tumor volume. ELISA method  was used to test the contents of survivin and cytochrome C(Cyt-C) in transplanted tumor tissue of mice. Reverse transcription polymerase chain reaction (RT-PCR) and Western blotting method  were used to detect the expression levels of Caspase-3, Bax and Bcl-2 mRNA and protein in transplanted tumor tissue of mice.   Results  Compared with the A group, the transplanted tumor tissue of mice in group B grew rapidly on day 7, 14, 21 and 28, the content of survivin was increased, the content of Cyt-C was decreased, the expression levels of Caspase-3 and Bax mRNA and protein was down-regulated, and the expression levels of Bcl-2 mRNA and protein was up-regulated (P<0.05, P<0.01). Compared with the B group, the transplanted tumor tissue of mice in group C and D grew slowly on day 14, 21 and 28, the content of survivin was decreased, the content of Cyt-C was increased, the expression levels of Caspase-3 and Bax mRNA and protein was up-regulated, and the expression levels of Bcl-2 mRNA and protein was down-regulated (P<0.05, P<0.01). There was no significant difference between group C and group D (P>0.05).   Conclusion  The role of IL-6 in promoting the growth and proliferation of pancreatic cancer may be related to the regulation of Caspase-3/Bax/Bcl-2 cell apoptosis signaling pathway.

Key words: Interleukin-6, Pancreatic cancer, MPC-83 cell, RT-PCR, Western blotting, Mouse

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