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DNMTi与HDACi对胆管癌细胞E-cadherin表达和细胞侵袭力的影响

Effects of DNA Methyltransferase Inhibitors and Histone Deacetylase Inhibitors on Expression of E-cadherin and Invasion of Cholangiocarcinoma Cell
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摘要 目的探讨联合使用DNA甲基化酶抑制剂(DNA methyltransferase inhibitor,DNMTi)和组蛋白脱乙酰化酶抑制剂(histone deacetylase inhibitor,HDACi)干预胆管癌细胞后,对E-cadherin基因的表达和细胞侵袭力的影响。方法根据给予胆管癌细胞不同的处理方法分为4组:空白对照组、肼屈嗪组、丙戊酸组和肼屈嗪+丙戊酸组,用RT-PCR、Western blot检测E-cadherin基因和蛋白的表达,用Transwell法检测细胞体外侵袭、转移力。结果空白对照组和丙戊酸组E-cadherin基因和蛋白均无表达,肼屈嗪+丙戊酸组E-cadherin基因和蛋白表达量均明显高于肼屈嗪组(P<0.01);同时肼屈嗪+丙戊酸组细胞的侵袭、转移力较空白对照组、丙戊酸组和肼屈嗪组明显下降(P<0.01)。结论DNMTi与HDACi协同恢复E-cadherin基因的表达,降低细胞侵袭、转移力,对于胆管癌的治疗有着重要的作用。 Objective To investigate the effects of DNA methyltransferase inhibitor (DNMTi) and histone deacetylase inhibitor (HDCAi) on expression of E-cadherin gene and invasiveness of cholangiocarcinoma cell. Methods According to different treatment, the QBC939 cells were divided into four groups: blank control group, hydralazine group, valproic acid group and hydralazine and valproic acid combined group. After 48 h, the expression of E-cadherin was evaluated by reverse transcription-PCR (RT-PCR), mehtylation specific PCR (MSP) and Western btot, the invasiveness of QBC939 cells was evaluated by Transwell method. Results There was no expression of E-cadherin mRNA and protien in blank control group and valproic acid group. The expressions of E-cadherin mRNA and protien in hydralazine and valproic acid combined group were higher than those in hydralazine group (P〈0.01), while the invasiveness of QBC939 cells of hydralazine and valproic acid combined group was much lower than that of blank control group, hydralazine group and valproic acid group (P〈0.01). Conclusion DNMTi and HDACi can synergistically re-express E cadherin gene and weaken the invasiveness of QBC939 cell, which plays an important part in treatment of cholangiocarcinoma.
出处 《中国普外基础与临床杂志》 CAS 2009年第1期44-47,51,共5页 Chinese Journal of Bases and Clinics In General Surgery
关键词 DNA甲基化酶抑制剂 组蛋白脱乙酰化酶抑制剂 DNA甲基化 DNA methyltransferase inhibitor Histone deacetylase inhibitor DNA methylation
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