凋亡抑制因子5在卵巢癌中的表达及临床意义

王娟 花晓棠*

doi:10.16098/j.issn.0529-1356.2017.03.009

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解剖学报 ›› 2017, Vol. 48 ›› Issue (3) : 303-309. DOI: 10.16098/j.issn.0529-1356.2017.03.009

肿瘤生物学

凋亡抑制因子5在卵巢癌中的表达及临床意义

王娟¹ 花晓棠^2*

作者信息 +

Expression and significance of apoptosis inhibitor 5 in ovarian cancer

WANG Juan¹ HUA Xiao-tang ^2*

Author information +

文章历史 +

摘要

目的检测凋亡抑制因子5（API5）在卵巢癌中的表达，分析其与临床病理特征的关系。方法 Western blotting方法检测2例正常卵巢组织及6例不同级别的卵巢癌组织的表达，组织化学方法检测10 例正常卵巢、119 例卵巢癌(浆液性腺癌61例、黏液性癌5例、内膜样癌10例、透明细胞癌10例及未分化癌33例) 组织中API5的表达，分析其表达与临床病理参数及5年生存率之间的相关性，细胞转染及凋亡流式细胞分析检测API5及顺铂对卵巢癌细胞的作用。结果 API5在卵巢癌组织中的表达高于正常卵巢组织，API5的表达与临床病例特征之间密切相关，Kaplan-Meier生存曲线揭示API5表达高的卵巢癌患者较低表达患者生存率低，流式细胞术分析显示，抑制API5的表达能增加顺铂对卵巢癌细胞的敏感性。结论 API5的异常表达与卵巢癌的发生密切相关，提示API5在预后评价中具有潜在的临床应用价值，有可能成为卵巢癌治疗的潜在靶点。

Abstract

Objective The study is designed to investigate the expression of apoptosis inhibitor 5（API5）in ovarian cancer（OC）, and to analysis its association with clinical pathologic variables. Methods API5 expression was evaluated by Western blotting in two normal ovarian tissues and six different fresh OC tissues. Immunohistochemistry analysis was performed on formalin-fixed paraffinembedded sections of 10 normal tissues and 119 cases of OCs (including 61 serous papillary adenocarcinoma, 10 endometrioid adenocarcinoma, 10 clear cell carcinoma, 5 mucinous papillary carcinoma, and 33 specimens were classified as undifferentiated carcinoma). SiRNA transfection and flow cytometry showed the impact of API5 and cisplatin on ovarian cancer cells. Results The expression of API5 was higher in the cancer samples compared with that in the normal ovary tissues. API5 was significantly associated with clinical pathologic variables(P<0.05). Kaplan-Meier curve showed that high expression of API5 was related to poor prognosis of OC patients than that low expression. Decreasing the expression of API5 enhanced EOC cell line’s sensibility to cisplatin by flow cytometry. Conclusion Our findings suggest that API5 is involved in the progression of OC and has a potential clinical application value in the assessment of prognosis, which may be a target of therapy in OC.

导出引用

王娟花晓棠. 凋亡抑制因子5在卵巢癌中的表达及临床意义[J]. 解剖学报. 2017, 48(3): 303-309 https://doi.org/10.16098/j.issn.0529-1356.2017.03.009

WANG Juan HUA Xiao-tang. Expression and significance of apoptosis inhibitor 5 in ovarian cancer[J]. Acta Anatomica Sinica. 2017, 48(3): 303-309 https://doi.org/10.16098/j.issn.0529-1356.2017.03.009

参考文献

［1］Siegel R, Ma J, Zou Z, et al. Cancer statistics, 2014［J］. CA Cancer J Clin, 2014, 64(1):9-29.

［2］Anuradha S,Webb PM, Blomfield P, et al. Survival of Australian women with invasive epithelial ovarian cancer: a population-based study［J］. Med J Aust, 2014, 201(5): 283-288.

［3］Garcia-Jove Navarro M, Basset C, Arconde’guy T, et al. Api5 contributes to E2F1 control of the G1/S cell cycle phase transition［J］. PLoeS One, 2013, 8(8):e71443.

［4］Gong YQ, Han FJ, Wu XK, et al. Progress in study on etiology of ovarian epithelial cancer［J］.Frontiers of Medicine, 2010，39(5):18-20. (in Chinese)

宫艳秋，韩凤娟，吴效科，等. 卵巢上皮性癌病因学研究进展［J］. 医学前沿，2010，39(5):18-20.

［5］Walters Haygood, CL, Arend RC, Straughn JM, et al. Ovarian cancer stem cells: Can targeted therapy lead to improved progression-free survival［J］? World J Stem Cells, 2014, 6(4):441-447.

［6］Ma RQ, Ye X, Cheng HY，et al. Expressions and clinical significance of ROBO4 in both serum and tumor tissues in patients with epithelial ovarian cancer［J］. Acta Anatomica Sinica, 2014, 45(1):64-69. (in Chinese)

马瑞琼，叶雪，程洪艳，等. ROBO4在上皮性卵巢癌组织和血清中的表达及临床意义［J］. 解剖学报，2014，45（1）：64-69.

［7］Lim S, Kaldis P. Cdks, cyclins and CKIs: roles beyond cell cycle regulation［J］. Development, 2013, 140(15):3079-3093.

［8］Stone A, Sutherland RL, Musgrove EA. Inhibitors of cell cycle kinases: recent advances and future prospects as cancer therapeutics［J］. Crit Rev Oncog, 2012,17(2):175-198.

［9］Zhao HL, Zhao XX, Wang YQ. The progress of API5［J］. Anhui Agricultural Science Bulleti, 2011，17(7):46. (in Chinese)

赵慧玲，赵鑫鑫，汪艳秋. API5相关的研究进展［J］. 安徽农学通，2011，17(7):46.

［10］Morris EJ, Michaud WA, Ji JY, et al. Functional identification of Api5 as a suppressor of E2F-dependent apoptosis in vivo［J］. PLoS Genet, 2006, 2(11):e196.

［11］Noh KH, Kim SH, Kim JH, et al. API5 confers tumoral immune escape through FGF2-dependent cell survival pathway［J］. Cancer Res, 2014, 74(13):3556-3566.

［12］Tewari M1, Yu M, Ross B, et al. AAC-11, a novel cDNA that inhibits apoptosis after growth factor withdrawal［J］. Cancer Res, 1997, 57(18):4063-4069.

［13］Kim JW, Cho HS, Kim JH, et al. AAC-11 overexpression induces invasion and protects cervical cancer cells from apoptosis［J］. Lab Invest, 2000, 80(4):587-594.

［14］Cho H, Chung JY, Song KH, et al. Apoptosis inhibitor-5 overexpression is associated with tumor progression and poor prognosis in patients with cervical cancer［J］. BMC Cancer, 2014, 14(1):545.

［15］Clegg N, Ferguson C, True LD, et al. Molecular characterization of prostatic small-cell neuroendocrine carcinoma［J］. Prostate, 2003, 55(1):55-64.

［16］Sasaki H, Moriyama S, Yukiue H, et al. Expression of the antiapoptosis gene, AAC-11, as a prognosis marker in nonsmall cell lung cancer［J］. Lung Cancer, 2001, 34(1):53-57.

［17］Wang Z, Liu H, Liu B, et al. Gene expression levels of CSNK1A1 and AAC-11, but not NME1, in tumor tissues as prognostic factors in NSCLC patients［J］. Med Sci Monit, 2010, 16(8):357-364.

［18］Li D, Liu Y, Li H, et al. MicroRNA-1 promotes apoptosis of hepatocarcinoma cells by targeting apoptosis inhibitor-5 (API-5)［J］. FEBS Lett, 2015, 589(1):68-76.

［19］Upraity S, Kazi S, Padul V, et al. MiR-224 expression increases radiation sensitivity of glioblastoma cells［J］. Biochem Biophys Res Commun, 2014, 448(2):225-230.

［20］Ren K, Zhang W, Shi Y, et al. Pim-2 activates API-5 to inhibit the apoptosis of hepatocellular carcinoma cells through NF-kappaB pathway［J］. Pathol Oncol Res, 2010,16(2):229-237.