[1]柴 婷,任 爽,张燕燕,等.抑制自噬对贝伐单抗诱导的结肠癌HCT116细胞凋亡的影响[J].郑州大学学报(医学版),2017,(03):356-359.[doi:10.13705/j.issn.1671-6825.2017.03.028]
 CHAI Ting,REN Shuang,ZHANG Yanyan,et al.Effect of autophagy inhibition on bevacizumab-induced apoptosis of human colon cancer HCT116 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2017,(03):356-359.[doi:10.13705/j.issn.1671-6825.2017.03.028]
点击复制

抑制自噬对贝伐单抗诱导的结肠癌HCT116细胞凋亡的影响()
分享到:

《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2017年03期
页码:
356-359
栏目:
应用研究
出版日期:
2017-05-15

文章信息/Info

Title:
Effect of autophagy inhibition on bevacizumab-induced apoptosis of human colon cancer HCT116 cells
作者:
柴 婷任 爽张燕燕匡 菁杨家梅#
郑州大学第二附属医院肿瘤科 郑州 450014
Author(s):
CHAI TingREN ShuangZHANG YanyanKUANG JingYANG Jiamei
Department of Oncology, the Second Affiliated Hospital, Zhengzhou University,Zhengzhou 450014
关键词:
自噬 贝伐单抗 结肠癌 凋亡
Keywords:
autophagy bevacizumab colon cancer apoptosis
分类号:
R735.3
DOI:
10.13705/j.issn.1671-6825.2017.03.028
摘要:
目的:探讨抑制自噬对贝伐单抗诱导的结肠癌HCT116细胞凋亡的影响。方法:用贝伐单抗、自噬抑制剂3-甲基腺嘌呤(3-MA)处理人结肠癌HCT116细胞48 h,Annexin V-FITC染色、流式细胞术检测细胞凋亡,吖啶橙染色、荧光显微镜观察细胞酸性自噬泡的变化,Western blot法检测细胞内自噬相关蛋白Beclin-1以及凋亡相关蛋白Caspase-9的表达。结果:贝伐单抗作用48 h对HCT116细胞的半数抑制剂量(IC50)为16 mg/L,3-MA的IC50为5 mmol/L。在此浓度下,3-MA单独作用可降低细胞中Beclin-1的表达,贝伐单抗单独作用可增强细胞中Beclin-1的表达,二者联用有拮抗作用(P<0.05)。3-MA和贝伐单抗单独作用均可提高细胞凋亡率(P<0.05),增强细胞中Caspase-9蛋白的表达(P<0.05),二者联用有协同作用(P<0.05)。结论:抑制自噬可增强贝伐单抗对结肠癌HCT116细胞的杀伤作用。
Abstract:
Aim: To study the effect of autophagy inhibition on bevacizumab-induced apoptosis of HCT116 cells.Methods: Human colon cancer HCT116 cells were treated with bevacizumab and autophagy inhibitor 3-methyl adenine(3-MA)alone or combined for 48 h, cell apoptosis rate was detected by Annexin V-FITC staining and flow cytometry, the changes of acidic autophagic vacuoles observed by acridine orange staining, the expressions of autophagy-related protein Beclin-1 and apoptosis-related protein Caspase-9 were detected by Western blot.Results: The median inhibition dose of bevacizumab for 48 h was 16 mg/L, and that of 3-MA was 5 mmol/L. At these doses,3-MA alone could decrease the expression of Beclin-1 in the cells(P<0.05), while bevacizumab alone could enhance Beclin-1 expression(P<0.05), and the effects of bevacizumab and 3-MA were antagonistic(P<0.05). 3-MA and bevacizumab alone could increase the apoptosis rate(P<0.05)and enhance the expression of Caspase-9 protein in the cells(P<0.05), and they had synergistic effect(P<0.05).Conclusion: Autophagy inhibition may enhance the killing effect of bevacizumab on the human colon cancer HCT116 cells.

参考文献/References:

[1] FERRARA N,HILLAN KJ,GERBER HP,et al.Discovery and development of bevacizumab, an anti-VEGF antibody for treating cancer[J].Nat Rev Drug Discov,2004,3(5):391
[2] THORBURN A,THAMM DH,GUSTAFSON DL.Autophagy and cancer therapy[J].Mol Pharmacol,2014,85(6):830
[3] GARG AD,DUDEK AM,FERREIRA GB,et al.ROS-induced autophagy in cancer cells assists in evasion from determinants of immunogenic cell death[J].Autophagy,2013,9(9):1292
[4] GARG AD,DUDEK AM,AGOSTINIS P.Autophagy-dependent suppression of cancer immunogenicity and effector mechanisms of innate and adaptive immunity[J].Oncoimmunology,2013,2(10):e26260
[5] PETROVSKI G,AYNA G,MAJAI G,et al.Phagocytosis of cells dying through autophagy induces inflammasome activation and IL-1β release in human macrophages[J].Autophagy,2011,7(3):321
[6] HANAHAN D,WEINBERG RA.Hallmarks of cancer:the next generation[J].Cell,2011,144(5):646
[7] 王营,郭志,倪虹.贝伐珠单抗治疗复发性卵巢癌的应用进展[J].肿瘤防治研究,2015,42(4):416
[8] 胡孟达.贝伐珠单抗联合 FOLFIRI 方案对于晚期 MCRC 患者的疗效及安全性分析[J].世界最新医学信息文摘,2016,16(78):7
[9] SANDLER A,GRAY R,PERRY MC,et al.Paclitaxel-carboplatin alone or with bevacizumab for non-small-cell lung cancer[J].N Engl J Med,2006,355(24):2542
[10]KLIONSKY DJ,ABDALLA FC,ABELIOVICH H,et al.Guidelines for the use and interpretation of assays for monitoring autophagy[J].Autophagy,2012,8(4):445
[11]RUBINSZTEIN DC,CODOGNO P,LEVINE B.Autophagy modulation as a potential therapeutic target for diverse diseases[J].Nat Rev Drug Discov,2012,11(9):U84
[12]CAREW JS,NAWROCKI ST,GILES FJ,et al.Targeting autophagy: a novel anticancer strategy with therapeutic implications for imatinib resistance[J].Biologics,2008,2(2):201
[13]VAZQUEZ-MARTIN A,OLIVERAS-FERRAROS C,MENENDEZ JA.Autophagy facilitates the development of breast cancer resistance to the anti-HER2 monoclonal antibody trastuzumab[J].PLoS One,2009,4(7):e6251

相似文献/References:

[1]单国用△,刘兴安,张松,等.食管鳞状细胞癌组织中自噬基因 Beclin 1蛋白的表达[J].郑州大学学报(医学版),2010,(03):366.
 SHAN Guoyong,LIU Xingan,ZHANG Song,et al.Expression of Beclin 1 protein in esophageal squamous cell carcinoma tissue[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2010,(03):366.
[2]周玉帅,殷竞争,张瑞锋,等.转染TDP25对SHSY5Y细胞自噬蛋白表达及细胞活力、凋亡的影响*[J].郑州大学学报(医学版),2015,(03):393.
 ZHOU Yushuai,YIN Jingzheng,ZHANG Ruifeng,et al.Expression of autophagy proteins and cell vitality,apoptosis of SHSY5Y cells transfected with TDP25[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2015,(03):393.
[3]王金兰,乐婷#,闫莹莹,等.阿托伐他汀对局灶性脑缺血大鼠脑组织中自噬及血管新生的影响[J].郑州大学学报(医学版),2016,(01):114.
 WANG Jinlan,YUE Ting,YAN Yingying,et al.Effect of atorvastatin on autophagy and angiogenesis in brain tissue of focal cerebral ischemia rats[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2016,(03):114.
[4]刘 端,李红雨,臧星卉,等.VEGF、MMP-9在卵巢癌组织中的表达及贝伐单抗联合顺铂对卵巢癌细胞SKOV3的作用[J].郑州大学学报(医学版),2018,(04):516.[doi:10.13705/j.issn.1671-6825.2017.11.088]
 LIU Duan,LI Hongyu,ZANG Xinghui,et al.Expressions of VEGF and MMP-9 in ovarian cancer tissue and effects of bevacizumab plus cisplatin on ovarian cancer SKOV3 cells[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2018,(03):516.[doi:10.13705/j.issn.1671-6825.2017.11.088]

备注/Memo

备注/Memo:
#通信作者,女,1965年12月生,硕士,主任医师,研究方向:肿瘤化疗,E-mail:yjm6601@163.com
更新日期/Last Update: 2017-05-20