卵巢肿瘤组织中抑癌基因ARHI的表达及组蛋白去乙酰化酶抑制剂对其的影响  

Expression of tumor suppressor gene ARHI in ovarian tumor and the effects of histone heacetylase inhibitors(HDACIs) on ARHI

作　　者：张兰[1] 刘培淑[1] 王秀英 辛刚[3] 

机构地区：[1]山东大学齐鲁医院妇产科,山东济南250012 [2]泰安市宁阳县人民医院妇产科,山东泰安271400 [3]山东大学第二医院妇产科,山东济南250033

出　　处：《山东大学学报（医学版）》2006年第12期1276-1280,共5页Journal of Shandong University:Health Sciences

摘　　要：目的:检测卵巢肿瘤组织中ARHI的表达,探讨组蛋白去乙酰化酶抑制剂曲谷抑菌素(TSA)对恶性卵巢肿瘤细胞生长抑制作用和基因表达的影响。方法:利用RT-PCR技术检测正常卵巢组织和卵巢肿瘤组织中ARHI mRNA的表达,比较ARHI基因表达与肿瘤良恶性、恶性肿瘤临床分期、组织分型的关系。利用MTT和RT-PCR检测组蛋白去乙酰化酶抑制剂TSA对4种卵巢癌细胞珠(SKOV3、A2780、COC1、OC3)的生长和ARHI基因表达的影响。结果:①正常卵巢组织中ARHI表达均为阳性(100%),卵巢良性肿瘤组织、交界性、恶性组织中不同程度表达缺失;②ARHI的表达与卵巢肿瘤的良恶性有关(P<0.05),与恶性肿瘤的组织学分型无关(P>0.05),与卵巢肿瘤临床分期有关(P<0.05);③4种卵巢癌细胞系中均未见ARHI表达,组蛋白去乙酰化酶抑制剂作用后仅SKOV3细胞系ARHI表达增强;④组蛋白去乙酰化酶抑制剂对卵巢肿瘤细胞生长有较明显抑制率且与浓度和时间有关(P<0.05),与顺铂比较,两者对4种细胞系的抑制率无明显差异(P>0.05)。结论:ARHI基因在卵巢肿瘤组织中有不同程度的低表达甚至缺失,与卵巢肿瘤的恶性程度有关。组蛋白去乙酰化酶抑制剂能有效抑制卵巢肿瘤细胞活性,是治疗肿瘤的新靶点。Objective： To investigate the expression of ARHI in ovarian tumor and the effects of histone deacetylase inhibitors（HDACIs） on the growth of ovarian cancer cells and the ARHI expression. Methods： mRNA expression of ARHI gene was evaluated in normal ovary and ovarian tumor by RT-PCR. And the effects of HDACIs on the expression of the ARHI in four ovrian cancer cells（SKOV3, A2780, COC1, OC3） was detected by RT-PCR and MTF. Results： （1）ARHI was expressed in all the normal ovarian tissues （100%）, but there was a different decline of ARHI gene in ovarian tumor; （2）The positive expression of ARHI was correlated with the malignant degree of tumor （ P 〈 0.05） and the clinical staging of ovarian cancer （ P 〈 0.05）, but not correlated with the his-grading parameters of cancer （P 〉0.05）; （3）No ARHI was found in four ovarian cancer cells. After infected with HDACIs, the expression of ARHI was up-regulated only in one cell, skov3; （4）HDACIs induced the apoptosis of cancer cells significantly, which inversely correlated with the density and time （P 〈 0.05）, while compared with the Cisplatin, there was not any histological differentiation （P 〉 0.05）. Conclusion： ARHI is expressed in normal ovarian cells, but is down-regulated or lost in ovarian tumor. HDACIs can inhibit the growth of cells and may be a new target for ovarian tumor.

关 键 词：卵巢肿瘤 ARHI 曲谷抑菌素 基因表达 

分 类 号：R737.31[医药卫生—肿瘤]