Sasaki T, Fujimoto Y, Tsuchida A, Kawasaki Y, Kuwada Y, Chayama K
First Department of Internal Medicine, Hiroshima University School of Medicine, Japan.
Pathobiology. 2001;69(5):258-65. doi: 10.1159/000064336.
In the present study, we examined the expression of peroxisome proliferator-activated receptor gamma (PPARgamma) in human pancreatic cancer and the possible effects of its ligand engagement on cell growth.
Seven human pancreatic cancer cell lines and 7 surgically resected human pancreatic cancer tissues were used as samples. The expression of PPARgamma was analyzed with reverse transcription-polymerase chain reaction and immunoblotting. The interaction between PPARgamma and PPAR-responsive element (PPRE) was examined by gel shift assay. Growth inhibition by thiazolidinediones was confirmed with anchorage-dependent and anchorage-independent growth assays.
PPARgamma was detected in all cell lines tested and in 5 out of 7 cancer tissues (71%), but was not found in adjacent normal pancreatic tissues. Gel shift analysis revealed that the proteins in nuclear extracts of the pancreatic cancer cell line PANC-1 specifically bind to the PPRE. Cell growth was significantly inhibited by treatment with troglitazone and rosiglitazone in a dose- and time-dependent manner (p < 0.01). In contrast, a nonfunctional metabolic analog of troglitazone did not affect cell growth.
These observations suggest that PPARgamma plays an important role in human pancreatic cancer growth and that ligand-induced activation of PPARgamma would be a useful strategy for treatment of human pancreatic cancer.
在本研究中，我们检测了过氧化物酶体增殖物激活受体γ（PPARγ）在人胰腺癌中的表达及其配体结合对细胞生长的可能影响。
以7种人胰腺癌细胞系和7例手术切除的人胰腺癌组织为样本。采用逆转录-聚合酶链反应和免疫印迹法分析PPARγ的表达。通过凝胶迁移试验检测PPARγ与PPAR反应元件（PPRE）之间的相互作用。噻唑烷二酮类药物对细胞生长的抑制作用通过贴壁依赖性和非贴壁依赖性生长试验得以证实。
在所检测的所有细胞系以及7例癌组织中的5例（71%）中检测到PPARγ，但在相邻正常胰腺组织中未检测到。凝胶迁移分析显示，胰腺癌细胞系PANC-1核提取物中的蛋白质能特异性结合PPRE。用曲格列酮和罗格列酮处理可显著抑制细胞生长，且呈剂量和时间依赖性（p < 0.01）。相比之下，曲格列酮的无功能代谢类似物不影响细胞生长。
这些观察结果表明，PPARγ在人胰腺癌生长中起重要作用，且配体诱导的PPARγ激活可能是治疗人胰腺癌的一种有效策略。
