Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARγ independent mechanisms
Antidiabetic thiazolidinediones inhibit invasiveness of pancreatic cancer cells via PPARγ independent mechanisms
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DOI：
10.1136/gut.2003.031997
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发表时间：
2004-11-01
期刊：
影响因子：
24.5
通讯作者：
Casini, A
中科院分区：
文献类型：
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作者：
Galli, A;Ceni, E;Casini, A
背景/目标：噻唑烷二酮类（TZD）是一类新型口服降糖药，已被证明可抑制某些上皮癌细胞的生长。虽然TZD被发现是过氧化物酶体增殖物激活受体γ（PPARgamma）的配体，但TZD发挥其抗癌作用的机制目前尚不清楚。此外，TZD对癌细胞的局部运动性和转移潜力的影响尚不清楚。作者分析了两个TZD，罗格列酮和吡格列酮，对人胰腺癌细胞系的侵袭力的影响，以评估这些药物在胰腺adenocarcinoma.Methods：人胰腺癌和胰腺癌细胞系中PPARgamma的表达通过逆转录聚合酶链反应测定，并通过蛋白质印迹分析证实。通过瞬时报告基因测定来评价PPARgamma活性。在改良的Boyden小室中进行侵袭测定。结果：TZD可抑制胰腺癌细胞的侵袭能力，影响明胶溶解和纤溶活性，其机制不依赖于激活PPARgamma，而与MMP-2和派-1的表达有关。TZD治疗胰腺癌细胞对生长和侵袭具有有效的抑制作用，这表明这些药物可能用于预防和治疗胰腺癌。人类胰腺癌
Background/Aims: Thiazolidinediones (TZD) are a new class of oral antidiabetic drugs that have been shown to inhibit growth of some epithelial cancer cells. Although TZD were found to be ligands for peroxisome proliferators activated receptor gamma (PPARgamma) the mechanism by which TZD exert their anticancer effect is currently unclear. Furthermore, the effect of TZD on local motility and metastatic potential of cancer cells is unknown. The authors analysed the effects of two TZD, rosiglitazone and pioglitazone, on invasiveness of human pancreatic carcinoma cell lines in order to evaluate the potential therapeutic use of these drugs in pancreatic adenocarcinoma.Methods: Expression of PPARgamma in human pancreatic adenocarcinomas and pancreatic carcinoma cell lines was measured by reverse transcription polymerase chain reaction and confirmed by western blot analysis. PPARgamma activity was evaluated by transient reporter gene assay. Invasion assay was performed in modified Boyden chambers. Gelatinolytic and fibrinolytic activity were evaluated by gel zymography.Results: TZD inhibited pancreatic cancer cells' invasiveness, affecting gelatinolytic and fibrinolytic activity with a mechanism independent of PPARgamma activation and involving MMP-2 and PAI-1 expression.Conclusion: TZD treatment in pancreatic cancer cells has potent inhibitory effects on growth and invasiveness suggesting that these drugs may have application for prevention and treatment of pancreatic cancer in humans.