[1]雷媛媛,张建伟,唐波,等.O-6-甲基鸟嘌呤-DNA甲基转移酶在顺铂激活的胃癌细胞自噬中的作用[J].第三军医大学学报,2018,40(04):290-295.
 LEI Yuanyuan,ZHANG Jianwei,TANG Bo,et al.Role of O-6-methylguanine-DNA methyltransferase in cisplatinactivated autophagy in human gastric cancer SGC-7901 cells[J].J Third Mil Med Univ,2018,40(04):290-295.
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O-6-甲基鸟嘌呤-DNA甲基转移酶在顺铂激活的胃癌细胞自噬中的作用(/HTML )
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《第三军医大学学报》[ISSN:1000-5404/CN:51-1095/R]

卷:
40卷
期数:
2018年第04期
页码:
290-295
栏目:
基础医学
出版日期:
2018-02-28

文章信息/Info

Title:
Role of O-6-methylguanine-DNA methyltransferase in cisplatinactivated autophagy in human gastric cancer SGC-7901 cells
作者:
雷媛媛张建伟唐波汪苏敏 吴玉云杨仕明
陆军军医大学(第三军医大学)第二附属医院消化内科
Author(s):
LEI Yuanyuan ZHANG Jianwei TANG Bo WANG Sumin WU Yuyun YANG Shiming

Department of Gastroenterology, Second Affiliated Hospital, Army Medical University (Third Military Medical University), Chongqing, 400037, China

关键词:
顺铂自噬DNA修复酶O-6-甲基鸟嘌呤-DNA甲基转移酶胃癌
Keywords:
cisplatin autophagy O-6-methylguanine-DNA methyltransferase gastric cancer
分类号:
R735.2;R966;R977.3
文献标志码:
A
摘要:

目的   探讨DNA修复酶O-6-甲基鸟嘌呤-DNA甲基转移酶(O-6-methylguanine-DNA methyltransferase, MGMT)在顺铂(cisplatin)激活的胃癌SGC-7901细胞自噬中的作用。方法    Western blot法检测自噬底物蛋白p62水平、自噬标志分子Ⅱ型和Ⅰ型微管相关蛋白轻链3(mircotuble-associated protein light chain 3,LC3)的比值变化、MGMT蛋白水平;GFP-LC3表达质粒转染胃癌SGC-7901细胞后用激光共聚焦显微镜观察顺铂对细胞自噬小体形成的影响。qRT-PCR法检测MGMT基因mRNA表达水平。结果    顺铂剂量依赖性激活胃癌SGC-7901细胞自噬水平,显著增加SGC-7901细胞中自噬小体数量;MGMT mRNA及蛋白水平随顺铂浓度的增加而降低(P<0.05);过表达MGMT抑制胃癌 SGC-7901 细胞的基础自噬水平;过表达MGMT抑制顺铂激活的胃癌SGC-7901细胞自噬。结论     DNA修复酶O-6-甲基鸟嘌呤-DNA甲基转移酶抑制顺铂激活的胃癌SGC-7901细胞自噬。

Abstract:

Objective    To investigate the role of O-6-methylguanine-DNA methyltransferase (MGMT) in autophagy activated by cisplatin in gastric cancer SGC-7901 cells. Methods     Western blotting was used to detect the baseline levels of autophagy substrate protein 62, microtubule-associated protein light chain 3-Ⅱ-and Ⅰ-ratio, and MGMT protein in human gastric cancer SGC-7901 cells. The effect of cisplatin on autophagy of the cells transfected with GFP-LC3 plasmid was observed with confocal laser scanning microscopy, and the mRNA expression of MGMT was examined with qRT-PCR. Results     Cisplatin activated autophagy in SGC-7901 cells in a dosedependent manner and significantly increased the formation of autophagosomes in the cells. The mRNA and protein levels of MGMT were decreased significantly in the cells as cisplatin dose increased (P<0.05). Overexpression of MGMT obviously suppressed both the basal level of autophagy and of cisplatin-activated autophagy in SGC-7901 cells. Conclusion     MGMT inhibits autophagy activated by cisplatin in gastric cancer SGC-7901 cells.

参考文献/References:

[1]JEMAL A, BRAY F, CENTER M M, et al. Global cancer statistics[J]. CA Cancer J Clin, 2011, 61(2): 69-90. DOI: 10.3322/caac.20107.
[2]ALMHANNA K. Targeted therapy for gastric adenocarcinoma[J]. Adv Pharmacol, 2012, 65: 437-470. DOI: 10.1016/B9780123979278.000142.
[3]CHOI A M, RYTER S W, LEVINE B. Autophagy in human health and disease[J]. New Engl J Med, 2013, 368(7): 651-662. DOI: 10.1056/NEJMra1205406.
[4]SHINTANI T, KLIONSKY D J. Autophagy in health and disease: a doubleedged sword[J]. Science, 2004, 306(5698): 990-995. DOI: 10.1126/science.1099993.
[5]ZHAO X, HE Y, CHEN H. Autophagic tumor stroma: mechanisms and roles in tumor growth and progression[J]. Int J Cancer, 2013, 132(1): 1-8. DOI: 10.1002/ijc.27664.
[6]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, 52(3): 356-359. DOI: 10.13705/j.issn.16716825.2017.03.028.
CHAI T, REN S, ZHANG Y Y, et al. Effect of autophagy inhibition on bevacizumabinduced apoptosis of human colon cancer HCT116 cells[J]. J Zhengzhou Univ(Med Sci), 2017, 52(3): 356-359. DOI: 10.13705/j.issn.16716825.2017.03.028.
[7]YAO C J, CHOW J M, CHUANG S E, et al. Induction of forkhead class box O3a and apoptosis by a standardized ginsenoside formulation, KG135, is potentiated by autophagy blockade in A549 human lung cancer cells[J]. J Ginseng Res, 2017, 41(3): 247-256. DOI: 10.1016/j.jgr.2016.04.003.
[8]HU F, GUO X L, ZHANG S S, et al. Suppression of p53 potentiates chemosensitivity in nutrientdeprived cholangiocarcinoma cells via inhibition of autophagy [J]. Oncol Lett,2017,14(2): 1959-1966. DOI: 10.3892/ol.2017.6449.
[9]CHEN Q C, YE L, FAN J J, et al. Autophagy suppression potentiates the antiglioblastoma effect of asparaginase in vitro and in vivo[J]. Oncotarget, 2017, 8: 91052-91066. DOI: 10.18632/oncotarget.19409.
[10]LIU J, CHEN Z, GUO J, et al. Ambra1 induces autophagy and desensitizes human prostate cancer cells to cisplatin [J]. Biosci Rep, 2017 Nov 3. pii: BSR20170770. DOI: 10.1042/BSR20170770. [Epub ahead of print]
[11]TRIMMER E E, ESSIGMANN J M. Cisplatin[J]. Essays Biochem, 1999, 34: 191-211. DOI: 10.1042/bse0340191.
[12]OLAUSSEN K A, DUNANT A, FOURET P, et al. DNA repair by ERCC1 in nonsmallcell lung cancer and cisplatinbased adjuvant chemotherapy[J]. New Engl J Med, 2006, 355(10): 983-991. DOI: 10.1056/NEJMoa060570.
[13]SATO K, KITAJIMA Y, NAKAGAWACHI T, et al. Cisplatin represses transcriptional activity from the minimal promoter of the O6methylguanine methyltransferase gene and increases sensitivity of human gallbladder cancer cells to 1(4amino2methyl5pyrimidinyl) methyl32chloroethyl)3nitrosourea[J]. Oncol Rep, 2005, 13(5): 899-906.
[14]王越, 刘春禹, 王增艳, 等. 土槿皮乙酸通过DNA损伤反应诱导细胞自噬来抑制凋亡[J]. 吉林中医药, 2017, 37(4): 381-384. DOI: 10.13463/j.cnki.jlzyy.2017.04.017.
WANG Y, LIU C Y, WANG Z Y, et al. Pseudolaric acid b induced autophagy through dna damage response to inhibit apoptosis[J]. Jilin J Tradit Chin Med, 2017, 37(4): 381-384. DOI: 10.13463/j.cnki.jlzyy.2017.04.017.
[15]LEI Y, ZHANG D, YU J, et al. Targeting autophagy in cancer stem cells as an anticancer therapy[J]. Cancer Lett, 2017, 393: 33-39. DOI: 10.1016/j.canlet.2017.02.012.
[16]SU Z, LI G, LIU C, et al. Autophagy inhibition impairs the epithelialmesenchymal transition and enhances cisplatin sensitivity in nasopharyngeal carcinoma [J]. Oncol Lett,2017,13(6): 4147-4154.DOI: 10.3892/ol.2017.5963.
[17]LI Y, JIANG W, HU Y, et al. MicroRNA199a5p inhibits cisplatininduced drug resistance via inhibition of autophagy in osteosarcoma cells[J]. Oncol Lett, 2016, 12(5): 4203-4208. DOI: 10.3892/ol.2016.5172.
[18]MA B, YUAN Z, ZHANG L, et al. Long noncoding RNA AC023115.3 suppresses chemoresistance of glioblastoma by reducing autophagy[J]. Biochim Biophys Acta, 2017, 1864(8): 1393-1404. DOI: 10.1016/j.bbamcr.2017.05.008.
 [19]DONG X, WANG Y, ZHOU Y, et al. Aquaporin 3 facilitates chemoresistance in gastric cancer cells to cisplatin via autophagy[J]. Cell Death Discov, 2016, 2: 16087. DOI: 10.1038/cddiscovery.2016.87.
[20]SHIN D, KIM E H, LEE J, et al. RITA plus 3MA overcomes chemoresistance of head and neck cancer cells via dual inhibition of autophagy and antioxidant systems[J]. Redox Biol, 2017, 13: 219-227. DOI: 10.1016/j.redox.2017.05.025.
[21]ZHU Q, LI H, LIU Y, et al. Knockdown of CFTR enhances sensitivity of prostate cancer cells to cisplatin via inhibition of autophagy[J]. Neoplasma, 2017, 64(5): 709-717. DOI: 10.4149/neo_2017_508.
[22]MIYAMOTO M, TAKANO M, AOYAMA T, et al. Inhibition of autophagy protein LC3A as a therapeutic target in ovarian clear cell carcinomas[J]. J Gynecol Oncol, 2017, 28(3): e33. DOI: 10.3802/jgo.2017.28.e33.
[23]LEE Y J, LEE G J, YI S S, et al. Cisplatin and resveratrol induce apoptosis and autophagy following oxidative stress in malignant mesothelioma cells[J]. Food Chem Toxicol, 2016, 97: 96-107. DOI: 10.1016/j.fct.2016.08.033.
[24]NIU Y, SUN W, LU J J, et al. PTEN Activation by DNA damage induces protective autophagy in response to cucurbitacin B in hepatocellular carcinoma cells[J]. Oxid Med Cell Longev, 2016, 2016: 4313204. DOI: 10.1155/2016/4313204.
[25]POLAGER S, OFIR M, GINSBERG D. E2F1 regulates autophagy and the transcription of autophagy genes[J]. Oncogene, 2008, 27(35): 4860-4864. DOI: 10.1038/onc.2008.117.

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更新日期/Last Update: 2018-02-28