泮托拉唑对胃癌细胞MKN-45增殖与凋亡的影响
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摘要
目的探讨泮托拉唑对胃癌细胞MKN-45增殖与凋亡的影响及相关机制。方法采用0、10、20、40μg/ml的泮托拉唑处理MKN-45细胞48 h;MTT法检测细胞活力;Hoechst染色检测细胞形态;流式细胞术检测细胞周期;Western blot检测细胞中B淋巴细胞瘤-2(Bcl-2)、Bcl-2相关X蛋白(Bax)、细胞周期蛋白D1(Cyclin D1)及Cyclin E表达。结果与0μg/ml比较,10、20、40μg/ml的泮托拉唑能明显降低MKN-45细胞活力(P﹤0.01),使细胞核发白,皱染,使细胞周期阻滞在G1期(P﹤0.01),下调Cyclin D1及Cyclin E的表达(P﹤0.01);与0μg/ml比较,20、40μg/ml的泮托拉唑能明显下调MKN-45细胞中Bcl-2的表达(P﹤0.01),上调Bax的表达(P﹤0.01)。结论泮托拉唑通过调控细胞周期蛋白及细胞凋亡相关蛋白表达抑制胃癌细胞MKN-45的增殖,并诱导细胞凋亡。
Objective To explore the effect of pantoprazole on the proliferation and apoptosis in gastric cancer cell MKN-45 and the underlying mechanism. Method MKN-45 cell was treated with 0, 10, 20, and 40 μg/ml pantoprazole for 48 h; cell viability was measured by MTT assay; cell morphology was detected by Hoechst staining; cell cycle was determined by flow cytometry; the expression of B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), Cyclin D1 and Cyclin E were measured by western blot. Result Compared with 0 μg/ml, treatment of 10, 20, 40 μg/ml pantoprazole reduced cell viability(P<0.01), resulting in dense and thick white cell nucleus, with cell cycle arrested in G1 phase(P<0.01), besides, the expression of Cyclin D1 and Cyclin E was down-regulated(P<0.01). 20 and 40 μg/ml pantoprazole might markedly down regulate the expression of Bcl-2(P<0.01), while up regulate the expression of Bax(P<0.01). Con Conclusion Pantoprazole could inhibit MKN-45 cell proliferation and induce cell apoptosis, by regulating expression of cell cyclin and apoptosis related protein.
Objective To explore the effect of pantoprazole on the proliferation and apoptosis in gastric cancer cell MKN-45 and the underlying mechanism. Method MKN-45 cell was treated with 0, 10, 20, and 40 μg/ml pantoprazole for 48 h; cell viability was measured by MTT assay; cell morphology was detected by Hoechst staining; cell cycle was determined by flow cytometry; the expression of B-cell lymphoma-2(Bcl-2), Bcl-2 associated X protein(Bax), Cyclin D1 and Cyclin E were measured by western blot. Result Compared with 0 μg/ml, treatment of 10, 20, 40 μg/ml pantoprazole reduced cell viability(P<0.01), resulting in dense and thick white cell nucleus, with cell cycle arrested in G1 phase(P<0.01), besides, the expression of Cyclin D1 and Cyclin E was down-regulated(P<0.01). 20 and 40 μg/ml pantoprazole might markedly down regulate the expression of Bcl-2(P<0.01), while up regulate the expression of Bax(P<0.01). Con Conclusion Pantoprazole could inhibit MKN-45 cell proliferation and induce cell apoptosis, by regulating expression of cell cyclin and apoptosis related protein.
引文
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[14]乔炜,琚坚,罗金波,等.胃癌相关基因及其在治疗中应用的研究进展[J].胃肠病学,2012,17(1):53-55.
[15]Sommariva S,Tarricone R,Lazzeri M,et al.Prognostic value of the cell cycle progression score in patients with prostate cancer:A Systematic Review and Meta-analysis[J].Eur Urol,2016,69(1):107-115.
[16]Cadoni G,Boccia S,Petrelli L,et al.A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes,cell cycle control and alcohol metabolism[J].Acta Otorhinolaryngol Ital,2012,32(1):1-11.
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[19]刘厚广,刘卓,姜颖,等.细胞周期蛋白与黑色素瘤的研究进展[J].中国地方病防治杂志,2015,30(1):30-33.
[20]游路宽,佘亚军,陈初鹏.细胞周期蛋白E1与恶性肿瘤关系的研究进展[J].癌变·畸变·突变,2016,28(6):487-490.
[2]邹文斌,李兆申.中国胃癌发病率及死亡率研究进展[J].中国实用内科杂志,2014,34(4):408-415.
[3]刘吉龙,文国容,金海,等.质子泵抑制剂抗胃癌的研究进展[J].医学综述,2017,23(4):670-674.
[4]翁涵,金海,庹必光.质子泵抑制剂抗肿瘤机制的研究进展[J].医学综述,2017,23(3):465-469.
[5]Ko Y,Tang J,Sanagapalli S,et al.Safety of proton pump inhibitors and risk of gastric cancers:review of literature and pathophysiological mechanisms[J].Expert Opin Drug Saf,2016,15(1):53-63.
[6]李浩,施芳红,刘菲,等.质子泵抑制剂与酸相关性疾病[J].世界华人消化杂志,2014,22(15):2073-2080.
[7]贺金凯,贺翠婷,刘鹰,等.质子泵抑制剂泮托拉唑的研究进展[J].中国药房,2016,27(26):3732-3735.
[8]van Rensburg CJ,Cheer S.Pantoprazole for the treatment of peptic ulcer bleeding and prevention of rebleeding[J].Clin Med Insights Gastroenterol,2012,5:51-60.
[9]蔡孝莉,冉丽丹,文国容,等.泮托拉唑对肝癌细胞SMCC-7721迁移、侵袭及凋亡的影响[J].中国医药导报,2015,12(13):7-10.
[10]Zeng X,Liu L,Zheng M,et al.Pantoprazole,an FDA-approved proton-pump inhibitor,suppresses colorectal cancer growth by targeting T-cell-originated protein kinase[J].Oncotarget,2016,7(16):22460-22473.
[11]Shen Y,Chen M,Huang S,et al.Pantoprazole inhibits human gastric adenocarcinoma SGC-7901 cells by downregulating the expression of pyruvate kinase M2[J].Oncol Lett,2016,11(1):717-722.
[12]廖毅,邓媛,傅建伟.胃癌分子机制的研究进展[J].中国肿瘤,2014,23(1):58-62.
[13]李加桩,王凯冰,郑红艳,等.胃癌分子靶向药物治疗的研究进展[J].中国肿瘤,2017,26(4):279-285.
[14]乔炜,琚坚,罗金波,等.胃癌相关基因及其在治疗中应用的研究进展[J].胃肠病学,2012,17(1):53-55.
[15]Sommariva S,Tarricone R,Lazzeri M,et al.Prognostic value of the cell cycle progression score in patients with prostate cancer:A Systematic Review and Meta-analysis[J].Eur Urol,2016,69(1):107-115.
[16]Cadoni G,Boccia S,Petrelli L,et al.A review of genetic epidemiology of head and neck cancer related to polymorphisms in metabolic genes,cell cycle control and alcohol metabolism[J].Acta Otorhinolaryngol Ital,2012,32(1):1-11.
[17]Hatok J,Racay P.Bcl-2 family proteins:master regulators of cell survival[J].Biomol Concepts,2016,7(4):259-270.
[18]Pietrantonio F,Biondani P,Ciurlia E,et al.Role of BAX for outcome prediction in gastrointestinal malignancies[J].Med Oncol,2013,30(3):610.
[19]刘厚广,刘卓,姜颖,等.细胞周期蛋白与黑色素瘤的研究进展[J].中国地方病防治杂志,2015,30(1):30-33.
[20]游路宽,佘亚军,陈初鹏.细胞周期蛋白E1与恶性肿瘤关系的研究进展[J].癌变·畸变·突变,2016,28(6):487-490.