中国癌症杂志 ›› 2019, Vol. 29 ›› Issue (4): 250-256.doi: 10.19401/j.cnki.1007-3639.2019.04.002

• 论著 • 上一篇    下一篇

前列腺癌中锌指蛋白ZIC2表达及对细胞增殖和凋亡的影响

张 能,苏 鹏,陈书练,李晓光,黄 翔,罗 旭   

  1. 遵义医学院附属医院泌尿外科,贵州 遵义 563003
  • 出版日期:2019-04-30 发布日期:2019-05-17
  • 通信作者: 罗 旭 E-mail:lx66989@qq.com
  • 基金资助:
    国家自然科学基金(81860524);贵州省科技厅研究项目(黔科合LH字[2014]7551号); 遵义医学院附属医院博士启动基金(院字[2014]5号)。

Expression of finger protein zinc finger protein ZIC2 and its effect on cell proliferation and apoptosis in prostate cancer

ZHANG Neng, SU Peng, CHEN Shulian, LI Xiaoguang, HUANG Xiang, LUO Xu   

  1. Department of Urology, the Affiliated Hospital of Zunyi Medical College, Zunyi 563003, Guizhou Province, China
  • Online:2019-04-30 Published:2019-05-17
  • Contact: LUO Xu E-mail: lx66989@qq.com

摘要: 背景与目的:锌指蛋白ZIC2在肿瘤中的表达及作用呈组织特异性,其异常表达与肿瘤的预后紧密相关。但ZIC2在前列腺癌中的表达与作用未见相应研究。该研究拟检测前列腺癌组织及细胞中ZIC2蛋白表达情况,明确ZIC2异常与临床病理参数间的关系与及对前列腺癌细胞增殖和凋亡的影响。方法:采用免疫组织化学SP法检测31例经穿刺活检诊断的前列腺癌标本及同期35例经尿道前列腺电切(transurethral resection of the prostate,TURP)获取的良性前列腺增生(benign prostatic hyperplasia,BPH)组织中ZIC2的表达,分析其异常表达与临床病理参数间的关系;应用小干扰RNA(small interfering RNA,siRNA)干扰ZIC2基因并转染前列腺癌DU145细胞,采用蛋白质印迹法(Western blot)检测蛋白水平。采用四甲基偶氮唑盐(methyl thiazolyl tetrazolium,MTT)法检测细胞增殖,采用流式细胞术检测细胞周期及细胞凋亡变化。结果:前列腺癌组织及BPH中ZIC2总阳性表达率分别为 90.32%(28/31)及20.00%(7/35),两者间差异有统计学意义(χ2=32.639,P=0.000)。ZIC2阳性表达率与前列腺癌 Gleason评分相关(χ2=9.753,P=0.003),与前列腺特异性抗原(prostate-specific antigen,PSA)、浸润深度无相关性(P均>0.05)。前列腺癌细胞中ZIC2表达明显升高,受干扰后蛋白显著降低;MTT法检测结果显示,ZIC2低表达后细胞生长明显减慢;流式细胞术检测结果显示,ZIC2降低后能有效抑制癌细胞增殖并增加凋亡。结论:ZIC2在前列腺癌中高表达,属癌基因,与Gleason评分密切相关;其表达降低后能有效抑制前列腺癌细胞增殖,诱导细胞凋亡。

关键词: 锌指蛋白ZIC2, 细胞增殖与凋亡, 前列腺癌

Abstract: Background and purpose: The expression and role of zinc finger protein ZIC2 are tissue-specific in various types of cancers, and its abnormal expression is closely related to the prognosis of tumors. However, there is no corresponding research on the expression and role of ZIC2 in prostate cancer. This study aimed to detect the expression of ZIC2 protein in prostate cancer tissues and cells, and to determine the relationship between ZIC2 abnormalities and pathological parameters and the effects on proliferation and apoptosis of prostate cancer cells. Methods: The expression of ZIC2 was detected using immunohistochemical SP method in the specimens from 31 cases of prostate cancer diagnosed by biopsy and 35 cases of benign prostatic hyperplasia (BPH) by transurethral resection of the prostate (TURP). The relationship between abnormal expression and clinicopathological parameters was analyzed. ZIC2 gene was treated with small interfering RNA (siRNA) in prostate cancer cells DU145, and protein expression of ZIC2 was verified by Western blot. Cell proliferation was detected by methyl thiazolyl tetrazolium (MTT). Cell cycle and apoptosis of prostate cancer cells were detected by flow cytometry. Results: The positive rates of ZIC2 expression in prostate cancer tissues and BPH were 90.32% (28/31) and 20.00% (7/35), respectively (χ2=32.639, P=0.000). The positive rate of ZIC2 expression was closely related to the Gleason score in prostate cancer specimens (χ2=9.753, P=0.003), while there was no exact correlation between prostate-specific antigen (PSA) and invasion depth of tumor (P>0.05). Due to ZIC2 being interfered by siRNA, the protein of ZIC2 was significantly decreased in prostate cancer cells. The results of MTT showed that the tumor growth was significantly slower following RNA interference, and the results of flow cytometry showed that ZIC2 could effectively inhibit the proliferation and promote apoptosis of prostate cancer cells. Conclusion: ZIC2 has increased expression in prostate cancer, and acts as an oncogene. ZIC2 expression is closely related to the Gleason score. Suppression of ZIC2 expression effectively inhibits proliferation of prostate cells and induces apoptosis.

Key words: Zinc finger protein ZIC2, Cell proliferation and apoptosis, Prostate cancer