Diterpenoid Tanshinone Attenuates the Metastasis of Non-small-cell Lung Cancer (NSCLC) Cells by Inhibiting the Cavin-1-mediated ERK/Smad2 Signaling Pathway.

BACKGROUND: Non-small cell lung cancer (NSCLC) is a common malignant cancer with high incidence and mortality. In recent decade, despite the progress in the treatment and prevention of NSCLC, its prognosis still remains poor. It is urgently needed to identify new potential mechanism and efficacious drugs for NSCLC patients. OBJECTIVE: 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. METHODS: 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. RESULTS: 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. CONCLUSION: Our results suggested that DT effectively attenuates Cavin-1-mediated NSCLC metastasis via the ERK/Smad2 signaling pathway.

Emodin inhibiting epithelial-mesenchymal transition in pulmonary fibrosis through the c-MYC/miR-182-5p/ZEB2 axis.

Emodin is a natural anthraquinone compound, which is the main component found in the traditional Chinese herb Polygonum cuspidatum. The anti-fibrosis effects of Emodin have been reported. This study aimed to explore the specific mechanism of Emodin in the epithelial-mesenchymal transition (EMT) of pulmonary fibrosis. The pulmonary fibrosis mice models were constructed with bleomycin, the EMT models of alveolar epithelial cells were stimulated by TGF-ß1, and Emodin was used for intervention. c-MYC and miR-182-5p were overexpressed or silenced by cell transfection. Our results demonstrated that Emodin attenuated pulmonary fibrosis induced by bleomycin in mice, and inhibited EMT, meanwhile downregulated c-MYC, upregulated miR-182-5p, and downregulated ZEB2 in vitro and vivo. Next, overexpression of c-MYC promoted EMT, while silencing c-MYC and overexpressing miR-182-5p inhibited EMT. Then, c-MYC negatively regulated the expression of miR-182-5p with a direct binding relationship. And miR-182-5p inhibited ZEB2 expression in a targeted manner. Finally, Emodin inhibited EMT that had been promoted by overexpression of c-MYC. In conclusion, Emodin could attenuate pulmonary fibrosis and EMT by regulating the c-MYC/miR-182-5p/ZEB2 axis, which might provide evidence for the application of Emodin in the treatment of pulmonary fibrosis.