PDB-1 from Potentilla discolor Bunge suppresses lung cancer cell migration and invasion via FAK/Src and MAPK signaling pathways

Abstract

Lung cancer is the primary reason of cancer death worldwide, with an annual incidence of ~1.3 million cases. Therefore, finding better and more effective methods to treat lung cancer has become very pressing. PDB-1 is a new C-27-carboxylated-lupane-triterpenoid derivative isolated from Potentilla discolor Bunge and is a type of compound that is rarely found in natural sources. This research investigated the effects of a novel triterpenoid compound PDB-1 on the expression of proteins regulating cancer proliferation, migration, and invasion in A549 and H460 cells. The results showed that PDB-1 inhibited the proliferation of A549 and H460 cells and that this inhibition was accompanied by decreased PCNA. Wound, transwell migration, and invasion assays showed that cell migration and invasion of lung cancer cells were significantly inhibited by PDB-1 in a dose-dependent manner. The results of western blot showed that PDB-1 decreased the level of p-FAK, which lead to the downregulation of MMP-2 and MMP-9 and decreased the potential for metastasis. Furthermore, after cells were treated with PDB-1, the expression levels of p-p38, p-ERK, and p-JNK were also dramatically decreased. Simultaneously, this study firstly showed that the PDB-1 can suppress the activation of the ERK/MAPK signaling pathway by inhibiting FAK expression, accordingly inhibiting the proliferation, migration, and invasion of lung cancer cells. Our study offered a molecular foundation for the potential application of PDB-1 on the therapy of lung cancer and the development of new antitumor drugs.