蓓萨罗丁通过激活ISGylation通路诱导乳腺癌MCF7细胞凋亡
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摘要
目的研究蓓萨罗丁通过ISGylation对乳腺癌细胞系凋亡的影响。方法通过不同浓度、不同时间的蓓萨罗丁处理MCF7细胞,用Annexin V-FITC/7-AAD法检测细胞凋亡情况。同时利用免疫印迹实验检测蓓萨罗丁诱导Cyclin D1下调的时间依赖性和浓度依赖性以及对ISGylation通路的依赖性。结果蓓萨罗丁可以促进MCF7细胞凋亡,下调Cyclin D1表达并在一定程度上依赖ISGylation。结论蓓萨罗丁可以通过ISGylation下调Cyclin D1表达并诱导乳腺癌细胞系凋亡,是乳腺癌的潜在治疗药物。
Objective To study the effects of bexarotene on apoptosis of breast cancer cell line MCF7 through ISGylation.Methods Apoptosis was detected by Annexin V-FITC/7-AAD kit after treated with bexarotene at different concentrations and different times.Western blotting was used to detect down-regulation of Cyclin D1 in time-dependent and concentration-dependent ways.The down-regulation also depended on ISGylation to some extent.Results Bexarotene can promote the apoptosis of MCF7 cells and down-regulate the expression of Cyclin D1 though ISGylation pathway.Conclusion Bexarotene can be a potential therapeutic drug for breast cancer by down-regulating Cyclin D1 though ISGylation and inducing apoptosis of breast cancer cell line.
Objective To study the effects of bexarotene on apoptosis of breast cancer cell line MCF7 through ISGylation.Methods Apoptosis was detected by Annexin V-FITC/7-AAD kit after treated with bexarotene at different concentrations and different times.Western blotting was used to detect down-regulation of Cyclin D1 in time-dependent and concentration-dependent ways.The down-regulation also depended on ISGylation to some extent.Results Bexarotene can promote the apoptosis of MCF7 cells and down-regulate the expression of Cyclin D1 though ISGylation pathway.Conclusion Bexarotene can be a potential therapeutic drug for breast cancer by down-regulating Cyclin D1 though ISGylation and inducing apoptosis of breast cancer cell line.
引文
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[2]付莉,王振宇,薛婷,等.乳腺癌相关遗传因素研究进展[J].国际遗传学杂志,2018,41(6):524-529.
[3]He Y,Liu Z,Qiao C,et al.Expression and significance of Wnt signaling components and their target genes in breast carcinoma[J].Mol Med Rep,2014,9(1):137-143.
[4]Arnold A,Papanikolaou A.Cyclin D1 in breast cancer pathogenesis[J].J Clin Oncol,2005,23(18):4215-4224.
[5]Musgrove E A,Caldon C E,Barraclough J,et al.Cyclin D as a therapeutic target in cancer[J].Nat Rev Cancer,2011,11(8):558-572.
[6]Santra M K,Wajapeyee N,Green M R.F-box protein FBX031 mediates cyclin D1 degradation to induce G1 arrest after DNA damage[J].Nature,2009,459(7247):722-725.
[7]Shan J,Zhao W,Gu W.Suppression of cancer cell growth by promoting cyclin D1 degradation[J].Mol Cell,2009,36(3):469-476.
[8]万越,陈守华,顾禾,等.硼替佐米联合表阿霉素对乳腺癌细胞增殖与凋亡的影响[J].山东大学学报(医学版),2012,50(2):43-46.
[9]姚峰,王冠楠,魏文,等.硼替佐米和3-甲基腺嘌呤对人乳腺癌细胞株MCF-7的抑瘤效应[J].微循环学杂志,2011,21(4):7-9.
[10]Gniadecki R,Assaf C,Bagot M,et al.The optimal use of bexarotene in cutaneous T-cell lymphoma[J].Br J Dermatol,2007,157(3):433-440.
[11]Feng Q,Sekula D,Guo Y,et al.UBE1L causes lung cancer growth suppression by targeting cyclin D1[J].Molecular Cancer Therapeutics,2008,7(12):3780-3788.
[12]Fritz H,Kennedy D,Fergusson D,et al.Vitamin A and retinoid derivatives for lung cancer:a systematic review and meta analysis[J].PloS one,2011,6(6):e21107.
[13]Huang M E,Ye Y C,Chen S R,et al.Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia[J].Blood,1988,72(2):567-572.
[14]Huang M E,Ye Y C,Chen S R,et al.Use of all-trans retinoic acid in the treatment of acute promyelocytic leukemia[J].Blood,1988,72(2):567-572.
[15]Zhang D,Zhang D E.Interferon-stimulated gene 15 and the protein ISGylation system[J].Journal of Interferon and Cytokine Research,2011,31(1):119-130.