PPAR-γ在肺癌中的表达及在肺癌凋亡中的作用研究

Expression of PPAR-γ and its apoptotic significance in lung cancer

背景与目的过氧化物酶体增生物激活受体(PPAR-γ)是对机体代谢过程起重要调节作用的一种核激素受体。研究表明肿瘤(包括肺癌)组织及细胞可表达PPAR-γ,且经其配体活化后可影响肿瘤细胞的分化、增殖及凋亡。本研究的目的是分析PPAR-γ的表达与肺癌临床病理特征之间的关系,并探讨PPAR-γ的配体对肺癌细胞生长的影响及其诱导凋亡的机制。方法采用免疫组化法检测15例非癌肺组织和64例肺癌组织中PPAR-γ的表达,并通过图像分析测定各组的平均吸光度值。采用RT-PCR和Western blot检测肺癌细胞株中PPAR-γ的表达。细胞经PPAR-γ的配体处理后,采用TUNEL法检测凋亡,并用caspase-3活性检测试剂盒检测其活性变化。结果PPAR-γ在肺癌组织中的表达显著高于非癌肺组织。PPAR-γ的表达与肿瘤病理类型、细胞分化程度、术后TNM分期有密切关系。肺癌细胞株中有PPAR-γ的表达,且经其配体活化后,caspase-3的活性明显增加,并能诱导细胞凋亡。结论PPAR-γ表达与肺癌的临床病理特征密切相关。活化后的PPAR-γ可使肺癌细胞caspase-3的活性增强,从而使细胞更易发生凋亡。PPAR-γ有可能成为未来肺癌诊断和治疗的一个新靶点。

Background and objective Peroxisome proliferato-activated receptor-gamma （PPAR-γ） is a kind of nuclear hormone receptor, which plays important roles in regulating metabolisms. Recently, PPAR-γ was found to express in tumor tissues and cells （including lung cancer）, which could be activated by its ligands and affect the differentiation, proliferation and apoptosis of tumor cells. The aim of this study is to investigate the relationship between PPAR-γ expression and clinicopathological characteristics of lung cancer, and to discuss the effect of PPAR-γ activators on lung cancer growth and the mechanisms of apoptosis induction for lung cancer. Methods Expression of PPAR-γ was detected in 15 non-cancerous pulmonary tissues and 64 lung cancer tissues by immunohistochemistry, and the average OD values were investigated by image analysis. Expression of PPAR-γ was detected in lung cancer cell lines by RT-PCR and Western blot. After treated with PPAR-γ activators, apoptosis of cells was detected by TUNEL, and caspase-3 activity was detected by using caspase 3 activity detection kit. Results Expression of PPAR-γ in lung cancer tissues was significantly higher than that in non-cancerous pulmonary tissues. Expression of PPAR-γ was closely related to histological classification, cell differentiation and TNM stages of lung cancer. PPAR-γ could express in two lung cancer cell lines, in which caspase-3 activity was significantly increased and obvious apoptosis was induced after treated with PPAR-γ activators. Conclusion PPAR-γ is closely associated with clinicopathological characteristics of lung cancer. Activated PPAR-γ can increase caspase-3 activity to induce apoptosis of cells. PPAR-γ may be a new target for diagnosis and treatment of lung cancer in the future.