Abstract
Although thiazolidinediones (TZDs) were found to be ligands for peroxisome proliferators-activated receptorγ (PPARγ), the mechanism by which TZDs exert their anticancer effect remains unclear. Furthermore, the effect of TZDs on metastatic and angiogenesis potential of cancer cells is unknown. Our results in this paper show that rosiglitazone inhibited SGC-7901 gastric cancer cells growth, caused G1 cell cycle arrest and induced apoptosis in a dose-dependent manner. The effects of rosiglitazone on SGC-7901 cancer cells were completely reversed by treatment with PPARγ antagonist GW9662. Rosiglitazone inhibited SGC-7901 cell migration, invasiveness, and the expression of MMP-2 in dose-dependent manner via PPARγ-independent manner. Rosiglitazone reduced the VEGF induced angiogenesis of HUVEC in dose-dependent manner through PPARγ-dependent pathway. Moreover, rosiglitazone did not affect the expression of VEGF by SGC-7901 cells. Our results demonstrated that by PPARγ ligand, rosiglitazone inhibited growth and invasiveness of SGC-7901 gastric cancer cells and angiogenesis in vitro via PPARγ-dependent or -independent pathway.
Highlights
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the ligand-inducible nuclear receptor superfamily
As a potential molecular target for anticancer drug development, peroxisome proliferators-activated receptorγ (PPARγ) and its ligands have been extensively studied in the past several years
Lu et al [10] found that PPARγ (+/−) mice were more susceptible to MNU-induced gastric cancer than wild-type (+/+) mice, and troglitazone significantly reduced the incidence of gastric cancer in PPARγ (+/+) mice but not in PPARγ (+/−) mice
Summary
Peroxisome proliferator-activated receptor gamma (PPARγ) is a member of the ligand-inducible nuclear receptor superfamily. Thiazolidinediones (TZDs) are synthetic agonists for PPARγ These PPARγ ligands were clinically used as antidiabetic drugs which could attenuate the insulin resistance associated with obesity, hypertension, and impaired glucose tolerance in humans [2]. Recent studies have suggested that PPARγ is a potential molecular target for anticancer drug development, due to the increased expression of PPAR in several cancer cells. Increasing evidence showed that TZDs are potential anticancer agents [3], the mechanisms underlying the antitumor effects are not well understood. TZDs were initially thought to inhibit the cancer cells proliferation through regulation of expression of PPARγ-mediated target genes. Recent evidence revealed that the antitumor effects of TZDs exist via PPARγ-independent mechanisms in various types of cancers [4,5,6]
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