Inhibitory Effects of Resveratrol on the Human Alveolar Rhabdomyosarcoma Cell Line PLA-802 through Inhibition of the TGF-β1/Smad Signaling Pathway

Abstract

While anti-tumor activity of resveratrol has been demonstrated for many cancers, little is known about its effects on soft tissue sarcoma. Overexpression of TGF-β1, a protein inhibited by resveratrol, is a well-known feature of the rhabdomyosarcoma (RMS), a type of soft tissue sarcoma. In the present study, we examined the effects of resveratrol on the human alveolar RMS (ARMS) cell line PLA-802. Cultured PLA-802 cells were treated with different concentrations of resveratrol at distinct time points and changes in their growth, cell cycle progression and TGF-β1 signaling were assessed. MTT assay showed a decrease in the viability of PLA-802 cells treated with resveratrol (p < 0.05). Cell cycle analysis using flow cytometry revealed that resveratrol induced a significant decrease in the number of cells in S phase and an increase in the number of cells in G1 phase (p < 0.05). Furthermore, expression of TGF-β1 and its downstream factor Smad4 mRNA and protein, assessed by RT-PCR and Western blot, were inhibited by resveratrol in a concentration- and time-dependent manner. Immunofluorescent staining results confirmed these changes in expression and showed that co-localization of TGF-β1 with Smad4 was gradually decreased by resveratrol. Together, our results suggest that resveratrol may inhibit cell proliferation and cell cycle progression in PLA-802 cells through inhibiting activity of the TGF-β1 signaling pathway. Our findings highlight the therapeutic potential of resveratrol for suppressing the tumorigenicity of human ARMS.