The effects and mechanisms of a biosynthetic ginsenoside 3β,12β-Di-O-Glc-PPD on non-small cell lung cancer.

BACKGROUND

A biosynthetic ginsenoside, 3-O-β-D-glucopyranosyl-12-O-β-D-glucopyranosyl-dammar-24-ene-3β, 12β, 20S-triol (CCPPD), showed antitumor activity against many tumor cells in vitro, especially had better anti-lung cancer activity than Rg3 in vitro and in vivo. However, the effects and molecular mechanisms of CCPPD on non-small cell lung cancer (NSCLC) remain unclear. According to previous studies, we hypothesized ginsenoside CCPPD could inhibit the tumor growth of NSCLC by targeting proliferation, migration and angiogenesis.

METHODS

A thiazolyl blue tetrazolium bromide assay (MTT) was performed to evaluate cell viability. Additionally, Transwell and tube formation assays were conducted to analyze cell migration and angiogenesis. The Lewis and A549 tumor xenograft experiments were also performed to investigate the effects of CCPPD on tumor growth in vivo, Western blotting and IHC assay were performed to analyze protein expression.

RESULTS

CCPPD could effectively inhibit the proliferation and migration of lung cancer cells, and tube formation of EA.hy926 cell. Ginsenoside CCPPD suppressed Lewis and A549 tumor growth in vivo without obvious side effects on body weight and the hematology index. In addition, the Western blot analysis revealed that the effects of CCPPD on lung cancer were mediated by inhibiting Raf/MEK/ERK, AKT/mTOR and AKT/GSK-3β/β-Catenin signaling pathways. Finally, CCPPD could significantly inhibit the proliferation index and vessel number in Lewis xenograft tumors analyzed by IHC.

CONCLUSION

The results of the present study suggest that ginsenoside CCPPD may serve as a potential therapeutic candidate compound against NSCLC.