奥巴克拉联合5-氟尿嘧啶对低氧性胰腺癌细胞上皮间质转化的影响

中国临床药理学与治疗学 ›› 2017, Vol. 22 ›› Issue (10): 1117-1122.

奥巴克拉联合5-氟尿嘧啶对低氧性胰腺癌细胞上皮间质转化的影响

侯新芳¹，宋海岩²，周志新³，邓晓慧²，张毅敏²，程慧欣⁴

¹郑州大学附属肿瘤医院河南省肿瘤医院肿瘤内科，郑州 450008，河南；²新乡医学院基础医学院，新乡 453003，河南；³新乡医学院期刊社《眼科新进展》编辑部，新乡 453003，河南；⁴新乡市中心医院病理科，新乡 453000，河南

收稿日期:2017-02-28 修回日期:2017-03-14 出版日期:2017-10-26 发布日期:2017-11-13
作者简介:侯新芳，女，博士，副主任医师，研究方向：肿瘤学。 Tel:15136130286 E-mail: houxinfang2013@163.com
基金资助:
河南省医学科技攻关计划项目（201702240）；新乡医学院科研培育基金（2014QN119）

Effects of obatoclax plus 5-Fluorouracil on the epithelial mesenchymal transition of pancreatic cancer cells under hypoxia

HOU Xinfang ¹, SONG Haiyan², ZHOU Zhixin³, DENG XiaoHui², ZHANG Yimin², CHENG Huixin ⁴

¹Department of Medical Oncology, Affiliated Cancer Hospital of Zhengzhou University, Zhengzhou 450008, Henan, China; ²School of Basic Medical Sciences, Xinxiang Medical University,Xinxiang 453003, Henan, China; ³ Editorial Department of Recent Advances in Ophthalmology, Xinxiang Medical University,Xinxiang 453003, Henan, China; ⁴ Department of Pathology, Xinxiang Central Hospital, Xinxiang 453000, Henan, China

Received:2017-02-28 Revised:2017-03-14 Online:2017-10-26 Published:2017-11-13

摘要/Abstract

摘要：

目的: 研究在低氧条件下，奥巴克拉(obatoclax)联合5-氟尿嘧啶(5-Fluorouracil，5-FU)对胰腺癌细胞株BxPC-3细胞上皮间质转化（epithelial mesenchymal transition, EMT）的影响。方法: 细胞分组为低氧组、5=FU组、obatoclax+5-FU组，利用MTT法检测各组BxPC-3细胞增殖活性；利用实时荧光定量PCR(RT-qPCR)与Western blot检测各组BxPC-3细胞中EMT相关基因与蛋白的表达情况。结果: 在低氧条件下，obatoclax联合5-FU可抑制BxPC-3细胞的增殖活性，且具有时间依赖性；obatoclax联合5-FU可进一步促进EMT的管家基因，转录因子Snail与Slug的表达升高；obatoclax联合5-FU促进上皮标记E-Cadherin的表达升高，及间质标记N-Cadherin、Fibronectin、Collagen I、Vimentin的表达下降。结论: 在低氧状态下obatoclax联合5-FU可抑制胰腺癌BxPC-3细胞的增殖活性，可通过抑制转录因子Snail与Slug的表达，上调上皮标记E-Cadherin的表达，下调间质标记N-Cadherin、Fibronectin、Collagen I及Vimentin的表达，从而抑制肿瘤细胞上皮向间质的转化，进而降低肿瘤细胞的迁移、侵袭能力。

关键词: 上皮间质转化, 低氧, 奥巴克拉, 5-氟尿嘧啶, 胰腺癌

Abstract:

AIM: To explore the effect of obatoclax combined with 5-Fluorouracil (5-FU) in epithelial mesenchymal transition(EMT) of pancreatic cancer BxPC-3 cells and its possible mechanism. METHODS: MTT assay was performed to detect cell viability in hypoxic group, 5-FU group and obatoclax combined with 5-FU group. RT-qPCR and Western blotting were used to detect EMT-related genes and proteins expression in BxPC-3 cells of hypoxic group, 5-FU group and obatoclax combined with 5-FU group. RESULTS: Under hypoxia condition, obatoclax combined with 5-FU time-dependently inhibited BxPC-3 cell proliferation activity. Obatoclax combined with 5-FU further down-regulated the expression of transcription factors Snail and Slug, as well as mesenchymal markers N-Cadherin, Fibronectin, Collagen I and Vimentin. Obatoclax combined with 5-FU up-regulated the expression of epithelial marker E-Cadherin. CONCLUSION: Under hypoxia condition, obatoclax combined with 5-FU inhibit the viability of BxPC-3 cells. Obatoclax combined with 5-FU can up-regulate E-Cadherin and down-regulate N-Cadherin, Fibronectin, Collagen I and Vimentin through inhibiting Snail and Slug, thus inhibiting EMT, reducing migration and invasion ability of BxPC-3 cells.

Key words: epithelial mesenchymal transition, hypoxia, obatoclax, 5-Fluorouracil, pancreatic cancer

中图分类号:

R965.2

侯新芳，宋海岩，周志新，邓晓慧，张毅敏，程慧欣. 奥巴克拉联合5-氟尿嘧啶对低氧性胰腺癌细胞上皮间质转化的影响[J]. 中国临床药理学与治疗学, 2017, 22(10): 1117-1122.

HOU Xinfang, SONG Haiyan, ZHOU Zhixin, DENG XiaoHui, ZHANG Yimin, CHENG Huixin. Effects of obatoclax plus 5-Fluorouracil on the epithelial mesenchymal transition of pancreatic cancer cells under hypoxia[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2017, 22(10): 1117-1122.

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