您的位置:山东大学 -> 科技期刊社 -> 《山东大学学报(医学版)》

山东大学学报(医学版) ›› 2017, Vol. 55 ›› Issue (1): 49-53.doi: 10.6040/j.issn.1671-7554.0.2016.1548

• 临床医学 • 上一篇    下一篇

肝X受体在卵巢癌组织中的表达及T0901317在卵巢癌细胞系SKOV3中的作用

赵路,矫俊,张腾,焦薪霖,崔保霞   

  1. 山东大学齐鲁医院妇产科, 山东 济南 250012
  • 收稿日期:2016-11-22 出版日期:2017-01-10 发布日期:2017-01-10
  • 通讯作者: 崔保霞. E-mail:cuibaoxia@163.com E-mail:cuibaoxia@163.com
  • 基金资助:
    山东省重点研发计划(2015GGE27352)

Expression of LXRα in ovarian carcinoma and effects of T0901317 on SKOV3 cell line

ZHAO Lu, JIAO Jun, ZHANG Teng, JIAO Xinlin, CUI Baoxia   

  1. Department of Obstetrics and Gynecology, Qilu Hospital of Shandong University, Jinan 250012, Shandong, China
  • Received:2016-11-22 Online:2017-01-10 Published:2017-01-10

摘要: 目的 检测肝X受体蛋白在卵巢癌组织及正常卵巢组织中的表达,探讨肝X受体激动剂T0901317对卵巢癌细胞系SKOV3细胞活力及凋亡的影响。 方法 收集2015年8月至2016年8月行初次手术治疗的51例卵巢癌患者的组织标本,另选取32例因子宫肌瘤等良性病变切除的正常卵巢组织作对照。采用免疫组织化学方法检测肝X受体蛋白在卵巢癌组织及正常卵巢组织中的表达;CCK8检测T0901317对卵巢癌细胞系SKOV3增殖的影响;流式细胞术检测T0901317对卵巢癌细胞系SKOV3凋亡的影响。 结果 肝X受体蛋白在正常卵巢组织较卵巢癌组织表达量高,两组比较差异有统计学意义(P<0.001),T0901317抑制卵巢癌细胞系SKOV3增殖具有明显的剂量依赖性和时间依赖性(P<0.05),T0901317促进SKOV3凋亡具有明显的剂量依赖性(P<0.05)。 结论 肝X受体表达下调可能与卵巢癌的发生发展有关,激活肝X受体可能会成为卵巢癌潜在的治疗靶点。

关键词: 增殖, 卵巢肿瘤, T0901317激动剂, 肝X受体, 凋亡

Abstract: Objective To detect the expression of liver X receptor α(LXRα)in normal ovarian tissues and ovarian cancer tissues, and to investigate the effects of the LXRs agonist T0901317 on SKOV3 cell line. Methods A total of 51 cases of ovarian cancer treated in our hospital during Aug. 2015 and Aug. 2016 were enrolled. Another 32 cases of benign ovarian lesions served as controls. The expression of LXRα was detected with immunohistochemistry. The proliferation of SKOV3 cell line treated with T0901317 was detected with CCK8 assay. The effect of T0901317 on the apoptosis of SKOV3 cell line was assayed with flow cytometry. Results There was significant difference in LXRα expression between normal ovarian tissues and ovarian cancer tissues(P<0.001). T0901317 significantly inhibited the proliferation of SKOV3 cell line in a dose- and time- dependent manner(P<0.05). Activation of LXRs could induce the apoptosis of SKOV3 cell line significantly(P<0.05). Conclusion The down-regulation of LXRs receptor may be related to the pathogenesis of ovarian cancer. For advanced ovarian cancer, activating LXR pathway is therefore a potential adjuvant therapy.

Key words: Ovarian cancer, Proliferation, Liver X receptors, Apoptosis, T0901317 agonist

中图分类号: 

  • R737.31
[1] Vaughan S, Coward JI, Bast RC Jr, et al. Rethinking ovarian cancer:recommendations for improving outcomes[J]. Nat Rev Cancer, 2011, 11(10):719-725.
[2] Siegel RL, Miller KD, Jemal A. Cancer statistics, 2015[J]. CA Cancer J Clin, 2015, 65(1):5-29.
[3] Kurman RJ, Shih IM. The origin and pathogenesis of epithelial ovarian cancer: a proposed unifying theory[J]. Am J Surg Pathol, 2010, 34(3):433-443.
[4] Jayson GC, Kohn EC, Kitchener HC, et al. Ovarian cancer[J]. Lancet, 2014, 384(9951):1376-1388.
[5] Grover VK, Valadez JG, Bowman AB, et al. Lipid modifications of sonic hedgehog ligand dictate cellular reception and signal response[J]. PLoS One, 2011, 6(7):e21353. doi:10.1371/journal.pone.0021353.
[6] 刘晓旺, 陆凯强, 熊婷, 等. 肝X受体—癌症治疗新靶点[J]. 临床与病理杂志, 2016, 36(5):690-694. LIU Xiaowang, LU Kaiqiang, XIONG Ting, et al. Liver X receptors—a new targets for cancer treatment[J]. Journal of Clinical and Pathological Research, 2016, 36(5):690-694.
[7] Ferlay J, Soerjomataram I, Dikshit R, et al. Cancer incidence and mortality worldwide:sources, methods and major patterns in GLOBOCAN 2012[J]. Int J Cancer, 2015, 136(5):71-96.
[8] Bast RC Jr, Hennessy B, Mills GB, et al. The biology of ovarian cancer:new opportunities for translation[J]. Nat Rev Cancer, 2009, 9(6):415-428.
[9] Zhang L, Reue K, Fong LG, et al. Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis[J]. Arterioscler Thromb Vasc Biol, 2012, 32(11):2541-2546.
[10] Raccosta L, Fontana R, Corna G, et al. Cholesterol metabolites and tumor microenvironment:the road towards clinical translation[J].Cancer Immunol Immunother,2016, 65(1):111-117.
[11] Zhang L, Reue K, Fong LG, et al. Feedback regulation of cholesterol uptake by the LXR-IDOL-LDLR axis. Arterioscler[J]. Arterioscler Thromb Vasc Biol, 2012, 32(11):2541-2546.
[12] Grover VK, Valadez JG, Bowman AB, et al. Lipid modifications of sonic hedgehog ligand dictatecellular reception and signal response[J]. PLoS One, 2011, 6(7):e21353. doi:10.1371/journal.pone.0021353.
[13] Wang Q, Sun L, Yang X, et al. Activation of liver X receptor inhibits the development of pulmonary carcinomas induced by 3-methylcholanthrene and butylated hydroxytoluene in BALB/c mice[J]. Sci Rep, 2016, 6:27295. doi:10.1038/srep27295.
[14] Savic D, Ramaker RC, Roberts BS, et al. Distinct gene regulatory programs define the inhibitory effects of liver X receptors and PPARG on cancer cell proliferation[J]. Genome Med, 2016, 8(1):74. doi:10.1186/s13073-016-0328-6.
[15] Nguyen-Vu T, Vedin LL, Liu K, et al. Liver x receptor ligands disrupt breast cancer cell proliferation through an E2F-mediated mechanism[J]. Breast Cancer Res, 2013, 15(3):R51. doi:10.1186/bcr3443.
[16] Krycer JR, Brown AJ. Does changing androgen receptor status during prostate cancer development impact upon cholesterol homeostasis?[J]. PLoS One, 2013, 8(1):e54007. doi:10.1371/journal.
[17] Scoles DR, Xu X, Wang H, et al. Liver X receptor agonist inhibits proliferation of ovarian carcinoma cells stimulated by oxidized low density lipoprotein[J]. Gynecol Oncol, 2010, 116(1):109-116.
[18] Rough JJ, Monroy MA, Yerrum S, et al. Antiproliferative effect of LXR agonist T0901317 in ovarian carcinoma cells[J]. J Ovarian Res, 2010, 3:13. doi:10.1186/1757-2215-3-13.
[19] Roshan-Moniri M, Hsing M, Butler MS, et al. Orphan nuclear receptors as drug targets for the treatment of prostate and breast cancers[J]. Cancer Treat Rev, 2014, 40(10):1137-1152.
[20] Nelson ER, Chang CY, McDonnell DP. Cholesterol and breast cancer pathophysiology[J]. Trends Endocrinol Metab, 2014, 25(12):649-655.
[21] De Boussac H, Alioui A, Viennois E, et al. Oxysterol receptors and their therapeutic applications in cancer conditions[J]. Expert Opin Ther Targets, 2013, 17(9):1029-1038.
[22] Nelson ER, Wardell SE, Jasper JS, et al. 27-Hydroxycholesterol links hypercholesterolemia and breast cancer pathophysiology[J]. In Science, 2013, 342(6162):1094-1098.
[23] Vedin LL, Lewandowski SA, Parini P, et al. The oxysterol receptor LXR inhibits proliferation of human breast cancer cells[J]. Carcinogenesis, 2009, 30(4):575-579.
[24] Chuu CP, Lin HP. Antiprolerative effect of LXR agonists T0901317 and 22(R)-hydroxycholesterol on multiple human cancer cell lines[J]. Anticancer Res, 2010, 30(9):3643-3648.
[25] 涂剑, 刘晓旺, 丁维珂, 等. T0901317促进人乳腺癌细胞凋亡的研究[J]. 中国临床药理学与治疗学, 2015, 50(12):1340-1347. TU Jian, LIU Xiaowang, DING Weike, et al. T0901 317 induces the apoptosis of MCF-7 and MDA-MB-231 human breast cancer cells[J]. Chinese Journal of Clinical Pharmacology and Therapeytics, 2015, 50(12):1340-1347.
[1] 王伟 王沂峰 张岭梅 林琼燕 黄菊. 人卵巢癌OVCAR3细胞系中侧群细胞的分离及其成瘤性、侵袭性的实验研究[J]. 山东大学学报(医学版), 2209, 47(6): 8-11.
[2] 张士宝 刘庆勇 阮喜云 陈杰 张建军 李宗武 杨广笑 王全颖. NT4-SAC-HA2-TAT融合基因表达载体的构建及鉴定[J]. 山东大学学报(医学版), 2209, 47(6): 15-19.
[3] 王晓磊 张海涛 张辉 郭成浩. 舒血宁注射液对高碘致培养血管内皮细胞损伤的保护作用[J]. 山东大学学报(医学版), 2209, 47(6): 38-.
[4] 鹿向东 杨伟 徐广明 曲元明. 脑膜瘤中PPAR-γ的表达及曲格列酮对脑膜瘤培养细胞生长的影响[J]. 山东大学学报(医学版), 2209, 47(6): 65-.
[5] 李涵,付婷婷,张磊,延冰,孙涛,郭峰,尹晓. 过氧化物酶增殖物激活受体γ激动剂对24例肥胖症患者米色脂肪细胞分化的影响[J]. 山东大学学报 (医学版), 2020, 1(9): 8-13.
[6] 孙薏丰,高玉,梁永媛,高杨. CPLX2在30例肝癌组织的表达及其对体外细胞增殖与侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(9): 34-39.
[7] 张宝文,雷香丽,李瑾娜,罗湘俊,邹容. miR-21-5p靶向调控TIMP3抑制2型糖尿病肾病小鼠肾脏系膜细胞增殖及细胞外基质堆积[J]. 山东大学学报 (医学版), 2020, 1(7): 7-14.
[8] 付洁琦,张曼,张晓璐,李卉,陈红. Toll样受体4抑制过氧化物酶体增殖物激活受体γ加重血脂蓄积的分子机制[J]. 山东大学学报 (医学版), 2020, 1(7): 24-31.
[9] 马青源,蒲沛东,韩飞,王超,朱洲均,王维山,史晨辉. miR-27b-3p调控SMAD1对骨肉瘤细胞增殖、迁移和侵袭作用的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 32-37.
[10] 李宁,李娟,谢艳,李培龙,王允山,杜鲁涛,王传新. 长链非编码RNA AL109955.1在80例结直肠癌组织中的表达及对细胞增殖与迁移侵袭的影响[J]. 山东大学学报 (医学版), 2020, 1(7): 38-46.
[11] 张亮,徐敏,庄向华,娄福臣,娄能俊,吕丽,郭文娟,郑凤杰,陈诗鸿. 内质网应激与凋亡在糖尿病周围神经病变中的表达变化[J]. 山东大学学报(医学版), 2017, 55(8): 13-17.
[12] 王凯民,谭娟娟,严志强,李志强. Sirtuin在低氧诱导人脐带间充质干细胞增殖中的作用[J]. 山东大学学报(医学版), 2017, 55(7): 23-30.
[13] 李睿,马伟红,任满意,赵萌萌,姜珊,巨媛媛,郭颖,孙昭辉,隋树建. TWEAK与原发性高血压患者心脏重塑的相关性[J]. 山东大学学报(医学版), 2017, 55(5): 49-55.
[14] 郭贺贺,孙志强,刘艳娟,刘奕晨,李广,郑方. 去甲斑蝥素对骨髓瘤U266细胞Notch信号通路表达的影响[J]. 山东大学学报(医学版), 2017, 55(3): 32-37.
[15] 史培堃,曾贝妮,吴伟芳,胡晓燕,马天加,周亚滨. Keap1在肾细胞癌中的表达及其作用[J]. 山东大学学报(医学版), 2017, 55(3): 94-99.
Viewed
Full text


Abstract

Cited

  Shared   
  Discussed   
No Suggested Reading articles found!