硼替佐米对胃癌细胞的抗肿瘤作用及其机制

摘要/Abstract

摘要： 目的: 观察硼替佐米对胃癌细胞的抗肿瘤作用,并探讨其相关的作用机制。方法: MTT生长抑制实验检测硼替佐米对胃癌SGC-7901细胞的细胞毒作用;PI和Annexin V-FITC双染流式细胞仪检测细胞凋亡情况;Western blot实验检测蛋白的表达变化。结果: 硼替佐米对胃癌SGC-7901细胞的IC₅₀值为(54.6±4.1) nmol/L。0、50、100 nmol/L 硼替佐米作用于SGC-7901细胞 48 h 后,细胞的凋亡率分别为(1.8±0.7)%、(26.5±4.6)%、(41.7±5.8)%,各组之间具有统计学差异(P<0.01)。50和 100 nmol/L 的硼替佐米作用SGC-7901细胞 48 h 后,细胞出现了Parp和caspase-3蛋白的裂解带。50和 100 nmol/L 的硼替佐米作用SGC-7901细胞 48 h 后,细胞Bmi-1蛋白的表达出现了显著的降低。结论: 硼替佐米对胃癌SGC-7901细胞具有显著的抗肿瘤活性,下调Bmi-1蛋白可能是其诱Anti-inflammatory effects of carboxyamidotriazole on carrageenan-induced acute inflammationZHU Lei, LI Juan, WU Dan-wei, YU Xiao-li, GUO Lei, YE Cai-ying, ZHANG De-changDepartment of Pharmacology, Institute of Basic Medical Sciences, Chinese Academy of Medical Sciences & School of Basic Medicine, Peking Union Medical College, Beijing 100005, ChinaABSTRACT AIM: To investigate the preventive effects of carboxyamidotriazole (CAI) in rat model of carrageenan-induced paw acute inflammation and its mechanisms.METHODS: The paw acute inflammation in rats was induced by carrageenan. The paw swelling was measured, and myeloperoxidase (MPO), NO, PGE₂, TNF-α, IL-1β, cytokine-induced neutrophil chemoattractant-1 (CNCI-1) and iNOS in the paw tissues were determined.RESULTS:CAI attenuated the carrageenan-induced paw swelling. CAI decreased the contents of MPO, NO, PGE₂, TNF-α, IL-1β and CNCI-1 in the inflamed paw tissues. Also, the protein expression of iNOS was reduced by CAI.CONCLUSION: CAI has anti-inflammatory effects against carrageenan-induced acute inflammation by decreasing the inflammatory mediators and the neutrophils infiltration.KEY WORDS Carboxyamidotriazole; Acute inflammation; Carrageenan; Myeloperoxidase; Inflammatory mediators 本文编辑:储冀汝导胃癌细胞凋亡的主要作用机制。

关键词: 胃癌, 硼替佐米, 细胞凋亡, Bmi-1

Abstract: AIM: To study the cytotoxic activity of bortezomib against gastric cancer and its action mechanism.METHODS: MTT assay was used to detect the cytotoxic activity of bortezomib against gastric cancer SGC-7901 cells. The apoptosis were detected by Annexin V-FITC/PI staining and flow cytometry analysis. The protein expressions were determined by Western blot analysis.RESULTS: The IC₅₀ value of bortezomib against SGC-7901 cells was (54.6± 4.1) nmol/L. After treatment with 0, 50, and 100 nmol/L bortezomib for 48 h, the percents of apoptosis were (1.8±0.7)% ,(26.5±4.6)%,(41.7±5.8) % , respectively. There was significant difference among the different treatments(P<0.01). After treatment with 50 and 100 nmol/L bortezomib for 48 h, the cleaved-Parp and cleaved-caspase-3 were detected by Western blot analysis. After treatment with 50 and 100 nmol/L bortezomib for 48 h, the protein expression of Bmi-1 was downregulated.CONCLUSION: Bortezomib shows significant anticancer activity against gastric cancer SGC-7901 cells. The downregulation of Bmi-1 protein may played an important role in its apoptotic pathway.

Key words: Gastric cancer, Bortezomib, Apoptosis, Bmi-1

中图分类号:

R965.2

陈辉, 瞿丽, 黄永刚. 硼替佐米对胃癌细胞的抗肿瘤作用及其机制[J]. 中国临床药理学与治疗学, 2013, 18(6): 606-609.

CHEN Hui, QU Li, HUANG Yong-gang. Cytotoxic activity of bortezomib against gastric cancer and its action mechanism[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(6): 606-609.

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