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Angiotensin II (Ang II)-elicited excessive proliferation, hypertrophy and migration of vascular smooth muscle cells (VSMCs) are vital to the pathogenesis of atheroclerosis. Glutathione S-transferase pi (GSTpi) exists extensively in various kinds of cells and protects cells against different stresses. However, knowledge remains limited about what GSTpi acts in VSMCs. We investigated the effect of GSTpi on Ang II-induced VSMC proliferation, hypertrophy and migration and its latent mechanism. Overexpression and RNAi experiments demonstrated that GSTpi inhibited Ang II-induced proliferation, hypertrophy and migration of VSMCs and arrested progression of cell cycle from G0/G1 to S phase. Immunoprecipitation, mass spectrometry and confocal microscopy analyses showed that GSTpi directly associated with signal transducer and activator of transcription 3 (STAT3) to prevent Ang II-triggered binding of Src to STAT3 and thus suppressed Ang II-stimulated phosphorylation and nuclear translocation of STAT3, as well as cyclin D1 expression. In contrast, GSTpi didn't affect Ang II-activated extracellular signal-regulated kinase (ERK1/2). GSTpi acts as a negative regulator to prevent Ang II-triggered proliferative signaling in VSMCs, suggesting that it may protect vessels against the stresses associated with atherosclerosis formation.

The activation of the hedgehog pathway, which is an important signaling mechanism crucial in embryogenesis, has strong links to carcinogenesis. Aberrant regulation of this pathway can result in the development of tumors. The present study was designed to investigate Hh related protein expression in non-small cell lung cancers. Fifty five non-small cell lung cancers samples were used in the study. By reverse transcription-polymerase chain reaction (RT-PCR), the expression of Shh, Ptch-1, and Gli-1 in tumor and adjacent normal tissues was examined and associated to clinical pathologic features. The expression levels of Shh, Ptch-1, Gli-1 in non-small cell lung cancer tissues were 63.64, 69.09, 43.64 %, respectively, higher than that in the adjacent normal tissues. Survival analysis showed that both Ptch-1 and Gli-1 expression were associated with poor survival (both P <0.05, log-rank test). Shh and Ptch-1 expression were correlated with lymph node metastasis. These results suggest that dysregulation of Hh signaling pathway plays an important role in the development of human NSCLCs. The expression of Ptch-1 and Gli-1 is possibly involved in NSCLCs progression, which may be a useful prognostic indicator of NSCLCs.