Inhibition of human lung cancer proliferation through targeting stromal fibroblasts by dihydromyricetin.

In the present study, the effects of dihydromyricetin on the proliferative potential of fibroblasts and lung carcinoma cells were investigated. Markedly higher expression levels of smooth muscle actin and platelet derived growth factors (PDGFs) were observed in the fibroblasts using reverse transcription-polymerase chain reaction analysis. The expression levels of PDGF-A and PDGF-B were also higher in the lung cancer cells. Western blot analysis revealed higher expression levels of the receptor for platelet-derived growth factor (PDGFRβ) in the lysates from fibroblasts obtained from normal tissues and carcinoma tissues. Treatment of the fibroblasts with dihydromyricetin inhibited the expression of PDGFRβ when treated with a 10 µM concentration for 48 h. Treatment of the fibroblasts with a 10 µM concentration of dihydromyricetin for 48 h led to complete inhibition of the activation of extracellular signal-regulated kinase (Erk)1/2 and Akt. The results of an MTT assay showed that treatment of the fibroblasts with dihydromyricetin significantly reduced the PDGF-mediated increase in the rate of proliferation. The rate of proliferation of the A549 lung cancer cells cultured with fibroblasts was markedly increased, compared with that of the A549 cells cultured alone. However, dihydromyricetin significantly (P<0.05) inhibited the proliferation rate of the A549 cells cultured with fibroblasts, compared with the untreated cultures. The proliferation rates of the A549 cancer cells, A549 cells cultured with fibroblasts, and A549 cells cultured with fibroblasts and treated with dihydromyricetin were found to be were 78.45, 98.45 and 21.37%, respectively. Dihydromyricetin inhibited the proliferative potential of fibroblasts in the lung cancer cells through targeting the activation of Erk1/2 and Akt. Therefore, there is scope for dihydromyricetin to be evaluated further for the treatment of lung cancer.