目的 探讨氧化应激在选择性环氧化酶-2抑制剂戊地昔布诱导人乳腺癌MCF-7/ADR细胞凋亡中的作用。方法 用噻唑蓝法检测药物对人乳腺癌MCF-7/ADR细胞生长的作用;用流式细胞仪和Hoechst 33258染色检测人乳腺癌MCF-7/ADR细胞凋亡;用试剂盒检测还原型谷胱甘肽和氧化型谷胱甘肽的含量;用激光共聚焦检测细胞内活性氧水平。结果 ①戊地昔布可诱导人乳腺癌MCF-7/ADR细胞凋亡,抑制细胞生长。②Caspase 3抑制剂Ac-DEVD-CHO和Caspase抑制剂Z-VAD-FMK可拮抗戊地昔布的作用。③戊地昔布可降低细胞还原型谷胱甘肽/氧化型谷胱甘肽比值,提高MCF-7/ADR细胞内的活性氧水平,抗氧化剂N-乙酰半胱氨酸可拮抗戊地昔布的抗肿瘤作用。结论 戊地昔布可诱导人乳腺癌MCF-7/ADR细胞凋亡,与其升高细胞内的活性氧有关。
Abstract
OBJECTIVE To study the effect of selective COX(cyclooxygenase)-2 inhibitor valdecoxib on the growth of human breast cancer MCF-7/ADR(MCF-7/adriamycin)cells. METHODS MTT assay was used to observe the effect of drugs on the growth of cells.Flow cytometry and Hoechst 33258 dye were used to detect apoptosis of MCF-7/ADR cells. The levels of GSH and GSSG were detected by kit; Laser confocal microscopy was used to detect the levels of ROS. RESULTS Valdecoxib significantly inhibited the growth of human breast cancer MCF-7/ADR cells and induced apoptosis of the cells. Caspase 3 inhibitor Ac-DEVD-CHO and caspase inhibitor Z-VAD-FMK antagonized the inhibitory effect of valdecoxib on MCF-7/ADR cell growth. Valdecoxib significantly decreased GSH/GSSG ratio and increased the level of ROS, and antioxidant N-acetylcysteine antagonized the inhibitory effect of valdecoxib on MCF-7/ADR cell growth.CONCLUSION The apoptosis of human breast cancer MCF-7/ADR cells induced by valdecoxib is associated with increase of ROS.
关键词
戊地昔布 /
环氧化酶-2 /
人乳腺癌MCF-7/ADR细胞 /
凋亡 /
活性氧
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Key words
valdecoxib /
cyclooxygenase-2 /
human breast cancer cell line MCF-7/ADR /
apoptosis /
reactive oxygen species
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中图分类号：
R965
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参考文献
[1] BAUMANN F T, BLOCH W, WEISSEN A, et al. Physical activity in breast cancer patients during medical treatment and in the aftercare——a review. Breast Care (Basel), 2013, 8(5):330-334.
[2] PRADOS J, MELGUIZO C, ORTIZ R, et al.Doxorubicin-loaded nanoparticles: New advances in breast cancer therapy. Anticancer Agents Med Chem, 2012, 12(9):1058-1070.
[3] XU Q H,HOU X M,WANG H C, et al. Effect of combination valdecoxib and pirarubicin on promoting apoptosis in human lung cancer cell. Chin Pharm J(中国药学杂志), 2013,48(12):972-975.
[4] GHOSH N, CHAKI R, MANDAL V, et al. COX-2 as a target for cancer chemotherapy. Pharmacol Rep, 2010, 62(2):233-244.
[5] WU W K, SUNG J J, LEE C W, et al. Cyclooxygenase-2 in tumorigenesis of gastrointestinal cancers: An update on the molecular mechanisms. Cancer Lett, 2010, 295(1):7-16.
[6] SANKARI S L, MASTHAN K M, BABU N A, et al.Apoptosis in cancer-an update. Asian Pac J Cancer Prev, 2012, 13(10):4873-4878.
[7] ZHONG X H, ZHAO L W, ZHAO F Q, et al.Effect of inotodiol on cell proliferation and apoptosis of human ovary cancer cell line SKOV3 and its molecular mechanism. Chin Pharm J(中国药学杂志),2014,49(3):191-194.
[8] MONIAN P, JIANG X. Clearing the final hurdles to mitochondrial apoptosis: Regulation post cytochrome C release. Exp Oncol, 2012, 34(3):185-191.
[9] ALLEN E M, MIEYAL J J.Protein-thiol oxidation and cell death: Regulatory role of glutaredoxins. Antioxid Redox Signal, 2012, 17(12):1748-1763.
GORRINI C, HARRIS I S, MAK T W.Modulation of oxidative stress as an anticancer strategy.Nat Rev Drug Discov, 2013, 12(12):931-947.
WANG H C, CHOUDHARY S. Reactive oxygen species-mediated therapeutic control of bladder cancer.Nat Rev Urol, 2011, 8(11):608-616.
PALOZZA P, PARRONE N, SIMONE R, et al. Role of lycopene in the control of ROS-mediated cell growth: Implications in cancer prevention. Curr Med Chem, 2011, 18(12):1846-1860.
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脚注
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基金
河北省科技攻关资助项目(07276403D);河北省卫生厅医学重点课题(2008067);河北省中医局课题(2009035)
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