脂质过氧化物酶体增殖物激活受体α在人肝癌多药耐药中的作用

Role of peroxisome proliferator-activated receptor α in multidrug resistance of human hepatocellular carcinoma

目的研究脂质过氧化物酶体增殖物激活受体α(peroxisome proliferator-activated receptor α,PPARα)在人肝癌多药耐药中的作用机制。方法利用透射电镜观察人肝癌多药耐药 (multidrug resistance,MDR)细胞HepG2／ADM及其亲本细胞HepG2的超微结构;荧光定量PCR技术检测PPARα mRNA在两种细胞系中的表达水平;免疫印记法检测PPARα蛋白的在两种细胞中的表达情况。结果人肝癌多药耐药细胞与其亲本细胞相比,耐药细胞的核膜上绒毛样突起增多,胞浆内有大量空泡,粗面内质网增多;HepG2／ADM细胞的PPARα mRNA表达和蛋白表达均有下降。结论PPARα与HepG2／ADM细胞的MDR现象有关,PPARα表达下调可能是肿瘤细胞MDR形成的机制之一。

Objective To study the role of PPARα gene in human hepatocellular carcinoma. Methods Transmission elctron microscopy was used to study the morphologic differences between the MDR cell line HepG2/ADM and its mother cell line HepG2 ; Real-time RT-PCR and Western blotting were used to check the expression of PPARα in mRNA level and protein level in the two cell lines respectively. Results Transmission elctron microscopy showed that the HepG2/ADM cells had more viliformed maculas on their nuclear memberanes, more vacuoles in their cytoplasmas, more rough endoplastic reticulums; the PPARα gene was down regulated in the HepG2/ADM cells. Conclusion PPARα is related with the muhidrug resistance phenomenon in the HepG2/ADM cells. The down regulation of PPARα may be one of the mechanisms conferring the forming of MDR in tumor cells.