Computational Molecular Docking and Cellular Evidence for Pioglitazone-Induced Adipogenic Differentiation in A549 Lung Adenocarcinoma Cells

초록

The present study examined adipogenic differentiation and growth inhibition in A549 lung adenocarcinoma cells cultured in adipogenic medium (AM; insulin, dexamethasone, and triiodothyronine) with or without pioglitazone (PGZ; 5 μM), a PPARγ agonist at a physiologically achievable plasma concentration. Human dermal fibroblasts (HDF) served as a normal cell reference. Proliferative capacity and lipid accumulation were assessed by population doubling time (PDT) and ORO staining over 3 weeks, and computational molecular docking was performed using AutoDock Vina (PDB: 5Y2O) with six ligands (four endogenous and two synthetic thiazolidinedione-class agonists). Both AM and AM+PGZ groups showed significantly increased PDT in A549 cells (P < .05), with AM+PGZ producing the most pronounced growth inhibition. In contrast, no significant differences were observed in HDF cells, confirming cancer cell-selective responses. ORO staining confirmed markedly elevated lipid accumulation in AM+PGZ-treated A549 cells. Pioglitazone showed the highest binding affinity (−8.794 kcal/mol; P<.001 versus each other ligand) and the lowest RMSD (2.207 Å) (not statistically significant), with key interactions at Cys285, Ser289, His323, and Tyr473 within the PPARγ ligand-binding domain. Although 5 μM pioglitazone alone is reportedly insufficient to induce adipogenic differentiation, its combination with adipogenic hormones drove substantial differentiation in the present study, consistent with a hormone-dependent lowering of the effective threshold for pioglitazone-induced adipogenic differentiation. These findings suggest that pioglitazone at a clinically relevant concentration may selectively promote adipogenic differentiation and suppress proliferation in A549 cells. As all evidence derives from a single cell line, this threshold effect remains a preliminary observation requiring further validation in vivo.

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