Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN
Peroxisome proliferator-activated receptor-γ inhibits pancreatic cancer cell invasion and metastasis via regulating MMP-2 expression through PTEN
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DOI：
10.3892/mmr.2015.4224
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发表时间：
2015-10-01
影响因子：
3.4
通讯作者：
Cao, Liang-Qi
中科院分区：
文献类型：
--
作者：
Li, Yue;Zhang, Da-Wei;Cao, Liang-Qi
胰腺癌的侵袭和转移行为与不良预后相关。因此，了解胰腺癌侵袭和转移的分子机制具有重要的理论和临床应用价值。近年来，随着对肿瘤发病机制的研究不断增多，人们发现过氧化物酶体增殖物激活受体-γ（PPARγ）和磷酸酶和张力蛋白同源物（PTEN）与胰腺癌的发生发展密切相关。因此，在本研究中，使用划痕实验、蛋白质印迹实验和transwell实验来研究它们的功能。划痕试验表明，用 PPAR γ 配体罗格列酮 (RGZ) 治疗可以减少胰腺癌细胞的运动和迁移。 Western blotting结果表明，RGZ抑制基质金属蛋白酶(MMP)-2的表达，而PPARγ抑制剂则促进MMP-2的表达。然而，PPARγ配体和抑制剂并不影响MMP-9的表达。进一步研究表明，PPAR γ 激活对 MMP-2 的调节是通过 PTEN 发生的。此外，PPARγ激活促进PTEN表达，从而抑制MMP-2的表达。随后的transwell实验表明，RGZ处理显着抑制了胰腺癌细胞的侵袭性，并且同时转染MMP-2过表达载体完全逆转了RGZ的抑制作用，从而增加了胰腺癌细胞的侵袭性。因此，PPARγ激活可以激活PTEN表达，从而抑制MMP-2的表达，从而抑制胰腺癌细胞的侵袭和转移。
The invasive and metastatic behavior of pancreatic cancer is associated with a poor prognosis. Therefore, understanding the molecular mechanisms underlying the invasion and metastasis of pancreatic cancer has important application values theoretically and clinically. In previous years, with increasing studies focusing on tumor pathogenesis, it has been revealed that peroxisome proliferator-activated receptor-gamma (PPAR gamma) and phosphatase and tensin homolog (PTEN) are closely associated with the occurrence and development of pancreatic cancer. Thus, in the present study, a scratch wound assay, western blotting and transwell assays were used to investigate their function. The scratch wound assay demonstrated that treatment with the PPAR gamma ligand rosiglitazone (RGZ) could reduce the movement and migration of pancreatic cancer cells. Western blotting results indicated that while RGZ inhibited the expression of matrix metalloproteinase (MMP)-2, PPAR gamma inhibitors promoted MMP-2 expression. However, PPAR gamma ligands and inhibitors did not affect the expression of MMP-9. Further investigation indicated that the regulation of MMP-2 by PPAR gamma activation occurred through PTEN. In addition, PPAR gamma activation promoted PTEN expression, thereby inhibiting the expression of MMP-2. Subsequent transwell experiments demonstrated that RGZ treatment significantly inhibited the invasiveness of pancreatic cancer cells and the inhibitory effect of RGZ was completely reversed by simultaneous transfection of the MMP-2-overexpressing vector, which increased the invasiveness of pancreatic cancer cells. Therefore, PPAR gamma activation can activate PTEN expression, thereby suppressing the expression of MMP-2 and hence inhibiting the invasion and metastasis of pancreatic cancer cells.