Diterpenoid tanshinone attenuates the metastasis of non-small-cell lung cancer (NSCLC) cells by inhibiting the Cavin-1-mediated ERK/Smad2 signaling pathway.

Abstract

The objective of this study is to explore the potential therapeutic role of diterpenoid tanshinone (DT) against non-small cell lung cancer (NSCLC) in vitro and elucidate the molecular mechanism involved in tumor metastasis. Human NSCLC lines (A549 and NCI-H1299) were transfected with pcDNA3.1-Cavin-1 plasmids and corresponding controls. We tested the effects of DT on migration and invasion of lung cancer cells using transwell filters coated with fibronectin and Matrigel. Next, Quantitative Real-Time PCR and western blot were used to determine the transcriptional and protein levels of epithelial-mesenchymal transition (EMT) markers, transcription factors (Snail, Slug), and matrix metalloproteinases. As expected, Cavin-1 related to the enhanced ability of cell migration and invasion. DT not only inhibited the migratory and invasive capacity of Cavin-1-transfected NSCLC cells but also significantly increased the expression of ZEB1 and E-cadherin and decreased the level of N-cadherin, Vimentin, Snail, and Slug. Moreover, DT treatment obviously alleviated Cavin-1 overexpression-induced high levels of MMP2, MMP7, and MMP9 at both the protein and transcriptional levels. Furthermore, overexpressed Cavin-1 upregulated ERK and Smad2 signaling pathways in NSCLC cells, which were also strongly weakened by DT administration. Our results suggested that DT effectively attenuates Cavin-1-mediated NSCLC metastasis via the ERK/Smad2 signaling pathway.