CD40调节胰腺癌细胞生物学行为的研究

doi:10.12092/j.issn.1009-2501.2018.07.006

中国临床药理学与治疗学 ›› 2018, Vol. 23 ›› Issue (7): 755-760.doi: 10.12092/j.issn.1009-2501.2018.07.006

CD40调节胰腺癌细胞生物学行为的研究

张桂枫¹，蔡加琴²，崔同建¹，刘振华¹，许志贤¹

¹福建省立医院，²福建医科大学省立临床学院，福州 350001，福建

收稿日期:2018-02-08 修回日期:2018-03-31 出版日期:2018-07-26 发布日期:2018-07-20
通讯作者: 许志贤，男，硕士，副主任医师，研究方向：消化道肿瘤。 Tel：13599395893 E-mail：xzx886@126.com
作者简介:张桂枫，女，硕士，副主任医师，研究方向：消化道肿瘤。Tel：13515029792 E-mail：984386537@qq.com
基金资助:
福建省卫生计生青年科研课题（2013037）；福建医科大学启航基金项目计划（2016QH106）

Effects of CD40 pathway on the biological behavior of pancreatic cancer cells

ZHANG Guifeng¹, CAI Jiaqin², CUI Tongjian¹, LIU Zhenhua¹, XU Zhixian¹

¹ Provincial Clinical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China；²Department of Pharmacy, Fujian Provincial Hospital, Fuzhou 350001, Fujian, China

Received:2018-02-08 Revised:2018-03-31 Online:2018-07-26 Published:2018-07-20

摘要/Abstract

摘要：

目的: 研究CD40L对胰腺癌细胞生物学特性、干性的影响。方法: CCK-8活细胞计数法分析CD40可溶性配体（sCD40L）不同浓度（0、1、2、4 μg/mL）在不同时间对人胰腺癌细胞系panc02生长增殖的影响，AnnexinV/PI双染法检测凋亡；细胞划痕实验检测迁移的改变。Q-PCR检测4 μg/mL sCD40L处理panc02 48 h后c-Myc、OCT-4、Sox-2水平的改变。建立Balb/c裸鼠胰腺癌荷瘤模型，随机分为2组，对照组（生理盐水）和sCD40L（10 mg/kg）组，分别腹腔注射sCD40L 10 mg/kg以及等体积生理盐水，每天注射3次，游标卡尺测量0、7、14、21、28 d时肿瘤体积。结果: 与对照组比较，浓度为1、2、4 μg/mL的sCD40L处理panc02 96 h时可显著抑制panc02的增殖（P＜0.01），并促进panc02的凋亡（P＜0.01），并呈剂量依赖性地抑制panc02的迁移能力（P＜0.01）；sCD40L 4 μg/mL组可明显抑制panc02细胞的c-Myc、OCT-4、Sox-2的表达（P＜0.01）。在裸鼠荷瘤实验中，与对照组比较，sCD40L处理28 d明显抑制肿瘤体积（P＜0.01，252±13 vs. 189±9）。结论: CD40通路的活化能够抑制胰腺癌细胞增殖迁移、促进凋亡，同时抑制胰腺癌细胞系体内的增殖能力，而这一效应可能与CD40L抑制胰腺癌细胞系干性相关。

关键词: 胰腺癌, 体内外增殖, CD40/CD40L, 干性

Abstract:

AIM: To study the effect of CD40L on the biological characteristics and stenness of pancreatic cancer cells. METHODS: The effect of different concentrations of sCD40L (0, 1, 2, 4 μg/mL) on the proliferation of human pancreatic cancer cell line panc02 was analyzed by CCK-8 live cell counting assay. Apoptosis was detected by Annexin V/PI double staining; migrational ability was detected by Cell Scratch Assays. Q-PCR was used to detect the levels of c-Myc, OCT-4 and Sox-2 after panc02 treatment for 4 h/mL sCD40L. A Balb/c nude mouse model of pancreatic cancer was established and randomly divided into two groups: control group (normal saline) and sCD40L (10 mg/kg) group. They were injected intraperitoneally with sCD40L 10 mg/kg and an equal volume of saline for three times a day. Tumor volume was measured using vernier calipers at 0, 7th, 14th, 21st, and 28th day. RESULTS: Compared with the control group, the growth and migration of panc02 decreased significantly after sCD40L treatment (1, 2, 4 μg/mL for 96 h), and apoptosis was promoted in a dose-dependent manner (P＜0.01). sCD40L (4 μg/mL) significantly inhibited the expression of c-Myc, OCT-4, Sox-2 of panc02 (P＜0.01). In the nude mice tumor-bearing experiment, compared with the control group, sCD40L significantly inhibited the tumor volume at 28th day (P＜0.01, 252±13 vs. 189±9). CONCLUSION: Activation of CD40 pathway inhibits proliferation, migration and apoptosis of pancreatic cancer cells as well as the proliferation of pancreatic cancer cell lines in vivo. This effect may be related to the change of stemness in pancreatic cancer cell lines.

Key words: pancreatic cancer, proliferation in vivo and in vitro, CD40/CD40L, stemness

中图分类号:

R965.2

张桂枫，蔡加琴，崔同建，刘振华，许志贤. CD40调节胰腺癌细胞生物学行为的研究[J]. 中国临床药理学与治疗学, 2018, 23(7): 755-760.

ZHANG Guifeng, CAI Jiaqin, CUI Tongjian, LIU Zhenhua, XU Zhixian. Effects of CD40 pathway on the biological behavior of pancreatic cancer cells[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2018, 23(7): 755-760.

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CD40调节胰腺癌细胞生物学行为的研究

Effects of CD40 pathway on the biological behavior of pancreatic cancer cells

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