SmacN7诱导乳腺癌细胞MDA-MB-157凋亡的作用及其机制*

doi:10.12047/j.cjap.5948.2020.134

中国应用生理学杂志 ›› 2020, Vol. 36 ›› Issue (6): 642-647.doi: 10.12047/j.cjap.5948.2020.134

SmacN7诱导乳腺癌细胞MDA-MB-157凋亡的作用及其机制^*

吕紫嫣⁺, 张肖艳⁺, 陈弘⁺, 蒋盼若, 陈佳玉^△

绍兴文理学院医学院, 浙江绍兴 312000

收稿日期:2019-10-08 修回日期:2020-11-12 出版日期:2020-11-28 发布日期:2021-03-15
通讯作者: ^△Tel: 0575-88345826; E-mail: chenkc1969@163.com.⁺: 为共同第一作者
基金资助:
^*国家自然科学基金资助项目(81402979);浙江省科技厅资助项目(2015C33270);浙江省卫生厅资助项目(2014KYA230);国家大学生创新创业训练计划项目(201810349028);浙江省大学生科技创新活动计划项目(2018R432016);绍兴市大学生创新项目(SXSDC201709)

Effects of SmacN7 inducing apoptosis of breast cancer cell MDA-MB-157 and its mechanism

LYU Zi-yan⁺, ZHANG Xiao-yan⁺, CHEN Hong⁺, JIANG Pan-ruo, CHEN Jia-yu^△

Medical school, ShaoxingUniversity, Shaoxing 312000, China

Received:2019-10-08 Revised:2020-11-12 Online:2020-11-28 Published:2021-03-15

摘要/Abstract

摘要： 目的:探讨SmacN7对乳腺癌细胞MDA-MB-157凋亡的作用及机制。方法:将0-20 μmol/L的SmacN7应用于乳腺癌细胞MDA-MB-157,用MTS法检测细胞增殖活性,流式细胞仪检测细胞凋亡、细胞周期,hoechst33342染色观察细胞核型变化,JC-1染色检测线粒体膜电位,LDH释放实验检测药物细胞毒性,qPCR检测各基因转录水平,并通过抑瘤实验证实该药抑制乳腺癌增殖的作用。结果:应用SmacN7后,乳腺癌细胞MDA-MB-157增殖抑制率和细胞凋亡率均增加(P＜0.01),核型发生显著变化,细胞线粒体膜电位降低,LDH释放量增加,并上调TRAIL、DR4、DR5、p53、PARP-1、Bax、Bid、BAK、caspase-3、caspase-8、caspase-9基因的转录水平(P＜0.01),下调 Ras、PI3K、AKT、mTOR、Bcl2、Bcl-xL、MCL-1、Survivin、cIAP-1、cIAP-2基因的转录水平(P＜0.01)。结论:SmacN7可通过TRAIL介导的死亡受体途径和线粒体介导的内源性凋亡途径诱导乳腺癌细胞MDA-MB-157凋亡,发挥抗乳腺癌的作用。

关键词: SmacN7, 乳腺癌, TRAIL通路, 线粒体凋亡途径, 细胞凋亡

Abstract: Objective: To investigate the effects and molecular mechanisms of Second mitochondria-derived activator of caspase N7 (SmacN7) on the apoptosis of breast cancer cells MDA-MB-157. Methods: Breast cancer cells MDA-MB-157 were treated with SmacN7 at the concentrations of 0-20 μmol/L. The proliferation activity of the cells was detected by MTS method, apoptosis and cell cycle were analyzed by flow cytometry, karyotypic changes of MDA-MB-157 cells were observed by Hoechst33342 staining, mitochondrial membrane potential was detected by JC-1 staining, and LDH release experiment was used to detect the drug cytotoxicity. Real time PCR was used to analyze the transcription levels of genes in MDA-MB-157 cells. The effect of inhibiting breast cancer proliferation was confirmed by tumor inhibition experiments. Results: After treated with SmacN7, the inhibition rate of proliferation and apoptosis rate of breast cancer cells MDA-MB-157 were increased (P＜0.01), the karyotype changed significantly, the mitochondrial membrane potential in cells was decreased, and the LDH release was increased. The transcription levels of TRAIL, DR4, DR5, p53, PARP-1, Bax, Bid, BAK, caspase-3, caspase-8 and caspase-9 were up-regulated (P＜0.01), and the transcription levels of Ras, PI3K, AKT, mTOR, Bcl-2, Bcl-xL, MCL-1, Survivin, cIAP-1 and cIAP-2 were inhibited (P＜0.01). Conclusion: SmacN7 induces apoptosis of breast cancer cell MDA-MB-157 through TRAIL-mediated death receptor pathway and mitochondrial-mediated endogenous apoptosis pathway, and plays a role in anti-breast cancer.

Key words: SmacN7, breast cancer, TRAIL pathway, mitochondrial pathway, cell apoptosis

中图分类号:

R737.9

吕紫嫣, 张肖艳, 陈弘, 蒋盼若, 陈佳玉. SmacN7诱导乳腺癌细胞MDA-MB-157凋亡的作用及其机制^*[J]. 中国应用生理学杂志, 2020, 36(6): 642-647.

LYU Zi-yan, ZHANG Xiao-yan, CHEN Hong, JIANG Pan-ruo, CHEN Jia-yu. Effects of SmacN7 inducing apoptosis of breast cancer cell MDA-MB-157 and its mechanism[J]. CJAP, 2020, 36(6): 642-647.

参考文献

[1] 郭艳婷, 王彦, 杜利清, 等. Tat-SmacN7对人乳腺癌细胞系的放射增敏作用[J]. 中华放射医学与防护杂志, 2014, 34(1): 13-17.
[2] 王彦, 杜利清, 徐畅, 等. Tat-SmacN7诱导肿瘤细胞辐射敏感性的机理研究 [J]. 辐射研究与辐射工艺学报, 2013, 31(6): 14-18.
[3] 杜亚南, 王彦, 刘强. Smac模拟物的抗肿瘤作用机制研究进展[J]. 国际生物医学工程杂志, 2017(1): 37-41.
[4] Zhang Y, Zhang G, Sun X, et al. Establishment of a murine breast tumor model by subcutaneous or orthotopic implantation[J]. Oncology Letters, 2018, 15(5): 6233-6240.
[5] Song JL, Chen C, Yuan JP, et al. Family history of cancer other than breast or ovarian cancer in first-degree relatives is associated with poor breast cancer prognosis[J]. Breast, 2017, 32: 130-134.
[6] Beberok A, Wrze＇sniok D, Rok J, et al. Ciprofloxacin triggers the apoptosis of human triple-negative breast cancer MDA-MB-231 cells via the p53/Bax/Bcl-2 signaling pathway[J]. Int J Oncol, 2018, 52(5): 1727-1737.
[7] 王振威, 肖刚, 刘威, 等. 不同基因分型乳腺癌中Caspase-3、XIAP、Smac表达情况及与临床病理参数的关系[J]. 实用癌症杂志, 2019, 34(1): 22-25.
[8] 徐聂, 李昌林, 肖敏伟, 等. 乳腺癌组织中Livin和Smac的表达及其临床意义[J]. 肿瘤预防与治疗, 2019, 32(4): 324-330.
[9] Kretz AL, Trauzold A, Hillenbrand A, et al. TRAIL blazing strategies for cancer treatment.[J]. Cancers (Basel), 2019, 11: 456.
[10] Duan ZG, Wei B, Deng JJ, et al. The anti-tumor effect of ginsenoside Rh4 in MCF-7 breast cancer cells in vitro and in vivo[J]. Biochem Biophys Res Commun, 2018, 499: 482-487.
[11] Lin SC, Chu PY, Liao WT, et al. Glycyrrhizic acid induces human MDA-MB-231 breast cancer cell death and autophagy via the ROS-mitochondrial pathway[J]. Oncology Reports, 2018, 39 (2): 703-710.
[12] 张雷, 程龙球, 周兆, 等. 双氢青蒿素对Raji细胞放射敏感性的影响[J]. 中国应用生理学杂志, 2017, 33(5): 385-390.
[13] Tseng HS, Wang YF, Tzeng YM, et al. Aloe-emodin enhances tamoxifen cytotoxicity by suppressing Ras/ERK and PI3K/mTOR in breast cancer cells[J]. Am J Chin Med, 2017, 45(2): 337-350.
[14] Jelinek M, Kabelova A, Sramek J, et al. Differing mechanisms of death induction by fluorinated taxane SB-T-12854 in breast cancer cells.[J]. Anticancer Res, 2017, 37(4): 1581-1590.
[15] Xue M, Ji X, Xue C, et al. Caspase-dependent and caspase-independent induction of apoptosis in breast cancer by fucoidan via the PI3K/AKT/GSK3β pathway in vivo and in vitro[J]. Biomed Pharmacother, 2017, 94: 898-908.
[16] Ward GA,LewisEJ,Ahn JS et al. ASTX660, a novel non-peptidomimetic antagonist of cIAP1/2 and XIAP, potently induces TNFα-dependent apoptosis in cancer cell lines and inhibits tumor growth.[J]. Mol Cancer Ther, 2018, 17: 1381-1391.
[17] Shi Z, Hodges VM, Dunlop EA, et al. Erythropoietin-induced activation of the JAK2/STAT5, PI3K/Akt, and Ras/ERK pathways promotes malignant cell behavior in a modified breast cancer cell line[J]. Mol Cancer Res, 2010, 8(4): 615-626.
[18] Serini S, Calviello G. Modulation of Ras/ERK and phosphoinositide signaling by long-Chain n-3 PUFA in breast cancer and their potential complementary role in combination with targeted drugs[J]. Nutrients, 2017, 9(3): 185.
[19] Costa RLB, Han HS, Gradishar WJ. Targeting the PI3K/AKT/mTOR pathway in triple-negative breast cancer: a review[J]. Breast Cancer Res Treat, 2018, 169(6): 1-10.
[20] 奉水东, 伍迪, 杨丝丝, 等. 槟榔碱对人乳腺癌MCF-7细胞增殖和凋亡的影响[J]. 中国应用生理学杂志, 2016, 32(4): 370-372.
[21] Moulder D, Hatoum D, Tay E, et al. The roles of p53 in mitochondrial dynamics and cancer metabolism: The Pendulum between survival and death in breast cancer[J] ? Cancers, 2018, 10(6): 189.

SmacN7诱导乳腺癌细胞MDA-MB-157凋亡的作用及其机制^*

Effects of SmacN7 inducing apoptosis of breast cancer cell MDA-MB-157 and its mechanism

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics

本文评价

[1]	王丹, 高峰, 陈慧, 项伟玲, 骆志显, 金丽琴. 人参归脾丸对脾不统血证大鼠肝损伤的保护作用及其机制^*[J]. 中国应用生理学杂志, 2020, 36(6): 571-575.
[2]	韩利蓉, 宋江勤, 郭飞波, 张栋武. miR-203a靶向及其靶基因对乳腺癌淋巴结转移的影响^*[J]. 中国应用生理学杂志, 2020, 36(6): 600-604.
[3]	张晓金, 张文霞, 朱吉玲, 罗文盼. 环状GMP-AMP合成酶高表达对乳腺癌细胞上皮间质转化的影响^*[J]. 中国应用生理学杂志, 2020, 36(4): 336-339.
[4]	刘凯丽, 都新新, 张文琴, 吴亚俐, 王茜, 王春芳, 崔香丽. 过表达miR-31对结肠炎模型小鼠TLR4/NF-κB信号通路及凋亡蛋白的调控[J]. 中国应用生理学杂志, 2020, 36(3): 211-215.
[5]	陈宇峰, 董凡赫, 楼云玮, 寿今豪, 张慧婷, 周一超, 严明, 毛红娇, 张云. 补骨脂素对TCP磨损颗粒所致大鼠成骨细胞损伤的干预作用及其机制[J]. 中国应用生理学杂志, 2020, 36(3): 255-260.
[6]	宋海岩, 张毅敏, 连辉, 周立. 低氧条件下奥巴克拉联合吉西他滨对乳腺癌细胞的作用[J]. 中国应用生理学杂志, 2020, 36(3): 268-272.
[7]	杲修杰, 王尚, 刘伟丽, 王坤, 陈照立, 王新兴. Sestrin2对热暴露肺上皮细胞凋亡的干预作用及其机制^*[J]. 中国应用生理学杂志, 2019, 35(4): 289-292.
[8]	洪凯, 蒋盼若, 柯瑞君, 应佳豪, 张肖艳, 陈佳玉. 2-12烷基-6-甲氧基环己基-2,5-二烯-1,4-二酮(DMDD)抗弥漫大B淋巴瘤的作用及机制^*[J]. 中国应用生理学杂志, 2019, 35(4): 312-316.
[9]	袁辉, 扬国宏, 李姝, 李丽, 宋高臣, 徐长庆, 孙健. 心肌梗死大鼠钙敏感受体表达与心肌细胞凋亡的变化[J]. 中国应用生理学杂志, 2019, 35(3): 268-272.
[10]	林中民, 陈国荣, 张泉波, 王芳, 项兰婷, 曹琼洁. 髓样分化蛋白2基因沉默对高糖诱导的大鼠心肌细胞增殖抑制、凋亡及炎症反应的影响^*[J]. 中国应用生理学杂志, 2019, 35(3): 273-278.
[11]	王瑜, 柯瑞君, 蒋盼若, 应佳豪, 楼恩哲, 陈佳玉. 杨芽黄素对前列腺癌细胞凋亡的影响及其机制^*[J]. 中国应用生理学杂志, 2019, 35(3): 283-288.
[12]	赵嘉涵, 贾雨涵, 汤雅婷, 林艺鑫, 王艳蕾. 参麦注射液对肠缺血/再灌注肺损伤大鼠肺组织p38MAPK及凋亡相关基因表达的影响[J]. 中国应用生理学杂志, 2019, 35(1): 65-68.
[13]	黄生辉, 巩婷, 李妍怡. 中风膏对氧糖剥夺/再复氧损伤大鼠海马神经干细胞增殖的影响[J]. 中国应用生理学杂志, 2018, 34(6): 554-557.
[14]	孙伟铭, 张源洲, 温馨, 席雨鑫, 袁迪, 王跃虹, 魏璨, 徐长庆, 李鸿珠. 外源性H₂S恢复缺氧后适应对衰老H9C2细胞的保护作用及机制[J]. 中国应用生理学杂志, 2018, 34(4): 289-293.
[15]	张瑞奎, 汪超. 苦参碱对大鼠乳腺癌细胞荷瘤生长及其炎性因子与免疫功能的影响[J]. 中国应用生理学杂志, 2018, 34(4): 375-378.