组蛋白去乙酰化酶抑制剂SAHA对卵巢癌SKOV3细胞的化疗增敏作用

doi:10.13481/j.1671-587x.20180303

吉林大学学报(医学版) ›› 2018, Vol. 44 ›› Issue (03): 471-476.doi: 10.13481/j.1671-587x.20180303

组蛋白去乙酰化酶抑制剂SAHA对卵巢癌SKOV3细胞的化疗增敏作用

梁冰¹, 刘扬², 宋金萍³, 曲丹华⁴, 刘纯岩⁵

1. 吉林大学护理学院妇产科护理教研室, 吉林长春 130021;
2. 吉林大学公共卫生学院放射医学实验教学中心, 吉林长春 130021;
3. 吉林大学基础医学院病理学与病理生理学系, 吉林长春 130021;
4. 吉林大学第二医院呼吸内科, 吉林长春 130041;
5. 吉林大学第二医院放射线科, 吉林长春 130041

收稿日期:2017-03-28 出版日期:2018-05-28 发布日期:2018-05-31
通讯作者: 刘纯岩,主管技师(Tel:0431-81136328,E-mail:xiaochunzi1@sohu.com);曲丹华,主管护师(Tel:0431-85619431,E-mail:61505502@qq.com) E-mail:xiaochunzi1@sohu.com;61505502@qq.com
作者简介:梁冰(1986-),女,吉林省长春市人,讲师,医学博士,主要从事肿瘤基因与放射治疗方面的研究。
基金资助:
国家自然科学基金青年基金资助课题（31700738）；中国博士后科学基金第九批特别资助课题（2016T90262）；中国博士后科学基金面上项目资助课题（2015M571372）；吉林大学白求恩医学部青年科研基金资助课题（2015440）

Enhancement of histone deacetylase inhibitors SAHA in chemotherapeutic sensitivity of ovarian cancer SKOV3 cells

LIANG Bing¹, LIU Yang², SONG Jinping³, QU Danhua⁴, LIU Chunyan⁵

1. Department of Obstetrics and Gynecology Care, School of Nursing, Jilin University, Changchun 130021, China;
2. Radiation Medicine Teaching Experiment Center, School of Public Health, Jilin University, Changchun 130021, China;
3. Department of Pathology and Pathophysiology, School of Basic Medical Sciences, Jilin University, Changchun 130021, China;
4. Departmentof Respiratory Medicine, Second Hospital, Jilin University, Changchun 130041, China;
5. Department of Radiology, Second Hospital, Jilin University, Changchun 130041, China

Received:2017-03-28 Online:2018-05-28 Published:2018-05-31

摘要/Abstract

摘要： 目的：探讨组蛋白去乙酰化酶抑制剂（HDACIs）辛二酰苯胺异羟肟酸（SAHA）联合长春新碱（VCR）对卵巢癌SKOV3细胞的生物学作用，并阐明其作用机制。方法：选择人卵巢癌SKOV3细胞，分为对照组、SAHA组、VCR组和SAHA+VCR组。CCK-8法检测各组SKOV3细胞生存率，流式细胞术（FCM）检测各组细胞凋亡率、自噬率和细胞周期分布情况。结果：CCK-8检测，与对照组比较，SAHA组和VCR组SKOV3细胞生存率明显降低；与SAHA或VCR组比较，SAHA+VCR组SKOV3细胞生存率明显降低（P<0.05）。FCM检测，与对照组比较，SAHA和VCR组SKOV3细胞凋亡率、自噬率及G₂/M期细胞百分率升高（P<0.05）；与SAHA或VCR组比较，SAHA+VCR组SKOV3细胞凋亡率、自噬率及G₂/M期百分率升高（P<0.05）。结论：SAHA可增强卵巢癌SKOV3细胞对VCR的敏感性，能够诱导SKOV3细胞凋亡与自噬，并促进G₂/M期阻滞；SAHA和化疗药物联合应用可能是治疗卵巢癌的新策略。

关键词: 卵巢肿瘤, 辛二酰苯胺异羟肟酸, 长春新碱, 敏感性

Abstract: Objective: To investigate the biological effects of histone deacetylase inhibitors(HDACIs) suberoylanilide hydroxamic acid(SAHA) combined with vincristine (VCR) on the ovarian cancer SKOV3 cells, and to clarify their mechanisms. Methods: The human ovarian cancer SKOV3 cells were divided into control group,SAHA group,VCR group and SAHA+VCR group.CCK-8 method was used to detect the surival rates of SKOV3 cells in various groups.The apoptotic rates,the autophagy rates and the distribution of cell cycles of SKVO3 cells in various groups were detected by flow cytometry (FCM). Results: The CCK-8 results showed that compared with control group,the survival rates of SKOV3 cells in SAHA group and VCR group were decreased significantly.Compared with VCR group or SAHA group,the survival rates of cells in SAHA+VCR groups were decreasedsignificantly(P<0.05).The FCM results demonstrated that compared with control group, the apoptotic rates,the autophagy rates and the percentages of the SKOV3 cells at G₂/M phase in SAHA group and VCR group were increased(P<0.05);compared with SAHA or VCR groups, the apoptotic rate,the autophagy rate and the percentages of SKOV3 cells at G₂/M phase in SAHA+VCR groups were increased(P<0.05). Conclusion: SAHA can enhance the sensitivity of ovarian cancer SKOV3 cells to VCR and induce the apoptosis and autophagy of SKOV3 cells to promote the cell arrest at G₂/M phase.The combined application of SAHA and chemotherapeutic drugs may be a new strategy for the treatment of ovarian cancer patients.

Key words: vincnistine, suberoylanilide hydroxamic acid, ovarian neoplasms, sensitivity

中图分类号:

R737.31

梁冰, 刘扬, 宋金萍, 曲丹华, 刘纯岩. 组蛋白去乙酰化酶抑制剂SAHA对卵巢癌SKOV3细胞的化疗增敏作用[J]. 吉林大学学报(医学版), 2018, 44(03): 471-476.

LIANG Bing, LIU Yang, SONG Jinping, QU Danhua, LIU Chunyan. Enhancement of histone deacetylase inhibitors SAHA in chemotherapeutic sensitivity of ovarian cancer SKOV3 cells[J]. Journal of Jilin University Medicine Edition, 2018, 44(03): 471-476.

参考文献

[1] Bast RC Jr,Hennessy B,Mills GB.The biology of ovarian cancer:New opportunities for translation[J].Nat Rev Cancer,2009,9(6):415-428.
[2] Ozols RF,Bookman MA,Connolly DC,et al.Focus on epithelial ovarian cancer[J].Cancer Cell,2004,5(1):19-24.
[3] Siegel R,Naishadham D,Jemal A.Cancer statistics,2013[J].CA Cancer J Clin,2013,63(1):11-30.
[4] Monk BJ,Coleman RL.Changing the paradigm in the treatment of platinum-sensitive recurrent ovarian cancer:from platinum doublets to nonplatinum doublets.and adding antiangiogenesis compounds[J].Int J Gynecol Cancer,2009,19 (suppl 2):S63-S67.
[5] Qin Y,Zhao X,Fang Y.PP242 synergizes with suberoylanilide hydroxamic acid to inhibit growth of ovarian cancer cells[J].Int J Gynecol Cancer,2014,24(8):1373-1380.
[6] Marks PA,Breslow R.Dimethyl sulfoxide to vorinostat:development of this histone deacetylase inhibitor as an anticancer drug[J].Nat Biotechnol,2007,25(1):84-90.
[7] Siegel D,Hussein M,Belani C,et al.Vorinostat in solid and hematologic malignancies[J].J Hematol Oncol,2009,2:31.
[8] Bolden JE,Peart MJ, Johnstone RW.Anticancer activities of histone deacetylase inhibitors[J].Nat Rev Drug Discov,2006,5(9):769-784.
[9] Olson DE,Sleiman SF,Bourassa MW,et al.Hydroxamate-based histone deacetylase inhibitors can protect neurons from oxidative stress via a histone deacetylase-independent catalase-like mechanism[J].Chem Biol,2015,22(4):439-445.
[10] Slingerland M,Guchelaar HJ,Gelderblom H.Histone deacetylase inhibitors:an overview of the clinical studies in solid tumors[J].Anticancer Drugs,2014,25(2):140-149.
[11] Emanuele S,Lauricella M,Tesoriere G.Histone deacetylase inhibitors:apoptotic effects and clinical implications(Review)[J].Int J Oncol,2008,33(4):637-646.
[12] Grabarska A,Luszczki JJ,Nowosadzka E,et al.Histone deacetylase inhibitor SAHA as potential targeted therapy agent for larynx cancer cells[J].J Cancer,2017,8(1):19-28.
[13] Fan M,Goodwin ME,Birrer MJ,et al.The c-Jun NH2-terminal protein kinase/AP-1 pathway is required for efficient apoptosis induced by vinblastine[J].Cancer Res,2001,61(11):4450-4458.
[14] Liang B,Liu X,Liu Y,et al.Inhibition of autophagy sensitizes MDR-phenotype ovarian cancer SKVCR cells to chemotherapy[J].Biomed Pharmacother,2016,82:98-105.
[15] Dietrich CS,Greenberg VL,DeSimone CP,et al.Suberoylanilide hydroxamic acid (SAHA) potentiates paclitaxel-induced apoptosis in ovariancancer cell lines[J].Gynecol Oncol,2010,116(1):126-130.
[16] Lee YJ,Won AJ,Lee J,et al.Molecular mechanism of SAHA on regulation of autophagic cell death in tamoxifen-resistant MCF-7 breast cancer cells[J].Int J Med Sci,2012,9(10):881-893.
[17] Chen MY,Liao WS,Lu Z,et al.Decitabine and suberoylanilide hydroxamic acid (SAHA) inhibit growth of ovarian cancer cell lines and xenografts while inducing expression of imprinted tumor suppressor genes,apoptosis,G₂/M arrest and autophagy[J].Cancer,2011,117(19):4424-4438.
[18] 王宝金,申爱荣,付喜玲,等.APTO-253 对紫杉醇或顺铂处理的卵巢癌 SKOV3 及 OVCAR3细胞凋亡及细胞周期的影响[J].郑州大学学报:医学版,2018, 53(1):75-79.

组蛋白去乙酰化酶抑制剂SAHA对卵巢癌SKOV3细胞的化疗增敏作用

Enhancement of histone deacetylase inhibitors SAHA in chemotherapeutic sensitivity of ovarian cancer SKOV3 cells

RichHTML

PDF (PC)

赞

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

Metrics

本文评价

推荐阅读 6

[1]	杨文延, 刘强, 孙志娟, 杜利清, 徐畅, 王彦, 柳杨, 王芹. 褪黑素对人非小细胞肺癌H1299细胞辐射敏感性的影响[J]. 吉林大学学报(医学版), 2018, 44(03): 532-536.
[2]	上官梦原, 赵菁, 杨艳荣, 张佳悦, 陈俊宇, 赵淑华. 五味子脂A联合卡铂对人卵巢癌Skov3细胞增殖、迁移和侵袭的抑制作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(02): 292-298.
[3]	钟莉莉, 赵银龙, 李炳锦, 邹晓晗, 程子倩, 崔然吉. MicroRNA-210对卵巢癌细胞生长及放射敏感性的影响[J]. 吉林大学学报(医学版), 2018, 44(02): 265-269.
[4]	上官梦原, 赵菁, 陈俊宇, 杨艳荣, 张佳悦, 赵淑华. 五味子脂A增强卡铂对人卵巢癌Skov3细胞的促凋亡作用及其机制[J]. 吉林大学学报(医学版), 2018, 44(01): 83-89.
[5]	王雪, 秦瑞, 王皓莹, 高守阳, 兰彦方, 田秀娟. 乳胞素联合卡铂对卵巢癌SKOV3细胞的增殖抑制作用和促凋亡作用[J]. 吉林大学学报(医学版), 2017, 43(06): 1098-1102.
[6]	邓子亮, 王森, 黎鹏, 解奎龙, 李淑贤, 周世雄, 贺晓舟, 陈东, 郭洪胜. 白细胞介素37对宫颈癌HeLa细胞顺铂化疗敏感性的增强作用[J]. 吉林大学学报(医学版), 2017, 43(05): 862-866.
[7]	任爱华, 王大伟. Hiwi基因靶向沉默对乳腺癌MCF-7/ADM细胞化疗敏感性的影响[J]. 吉林大学学报(医学版), 2017, 43(04): 743-746.
[8]	赫东芸, 王立岩, 盛敏佳. 预防性输卵管切除术对卵巢功能的影响及其对盆腔疾病的预防作用[J]. 吉林大学学报(医学版), 2017, 43(03): 635-639.
[9]	杨耀群, 谢淑丽, 吕国悦, 马强, 李开良, 王广义. 肝癌SMMC7721细胞株P27RF-Rho mRNA基因沉默对5-Fu药物敏感性的影响[J]. 吉林大学学报(医学版), 2017, 43(02): 271-275.
[10]	王立岩, 张贝贝, 赫东芸, 盛敏佳, 王雪. 二甲双胍和紫杉醇对卵巢癌SKOV3细胞体外增殖和凋亡的影响[J]. 吉林大学学报(医学版), 2017, 43(02): 255-259.
[11]	王睿斌, 赫东芸, 邹积艳, 盛敏佳. DC-CIK免疫治疗对卵巢癌患者凝血功能及D-二聚体水平的影响[J]. 吉林大学学报(医学版), 2017, 43(01): 120-124.
[12]	张玉宇, 王利波, 赵钦, 李戈, 龚守良, 董丽华. 肿瘤微环境与肿瘤细胞放射敏感性关系的研究进展[J]. 吉林大学学报(医学版), 2016, 42(05): 1038-1044.
[13]	汪海娇, 范艳艳, 张湜, 张瑞丽, 张海静, 韩亚辉, 朱继红. γδT细胞对卵巢癌SKOV3细胞增殖的抑制作用[J]. 吉林大学学报(医学版), 2016, 42(05): 897-900.
[14]	盛敏佳, 刘津, 刘俊宝, 邹积艳. 褪黑素联合卡铂对卵巢癌SKOV3细胞体外增殖及凋亡的影响[J]. 吉林大学学报(医学版), 2016, 42(01): 70-75.
[15]	王堃, 张爱臣, 盛敏佳, 潘颖, 佟玲玲, 孙小淳. 骨桥蛋白和趋化因子受体4在卵巢肿瘤组织中的表达及其意义[J]. 吉林大学学报(医学版), 2015, 41(06): 1186-1189.