Tanshinone IIA affects the proliferation of A549/Tax by affecting the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway.

Abstract

Objective: This study aims to explore whether tanshinone IIA can act on paclitaxel-resistant non-small cell lung cancer A549/Tax and analyze the possible mechanisms involved.

Methods: Using the Cell Counting Kit-8 (CCK-8), we preliminarily analyzed whether tanshinone IIA has an inhibitory effect on A549/Tax cells. We utilized public datasets, self-collected transcriptome datasets, and drug target analysis to identify potential targets. We employed real-time fluorescent quantitative polymerase chain reaction (RT-qPCR) to detect the expression of core genes before and after drug treatment to analyze potential target genes and validated them using data from The Cancer Genome Atlas (TCGA). We conducted enrichment analysis on co-expressed genes of the target genes to explore potential mechanisms. Furthermore, we employed molecular docking and western blot to verify the possible mechanisms involved.

Results: The CCK8 results indicated that tanshinone IIA has a significant inhibitory effect on A549/Tax cells. The qPCR results and the analysis of TCGA data indicated that MMP7 is the target gene. Enrichment results of MMP7 co-expressed genes suggested that the PI3K-AKT signaling pathway might play a key role. Molecular docking results indicated that tanshinone IIA has strong binding activity with PI3K, AKT, mTOR, and MMP7. Western blotting results showed that tanshinone IIA might inhibit MMP7 through the PI3K-AKT-mTOR signaling pathway.

Conclusions: Tanshinone IIA may affect the proliferation of A549/Tax by influencing the expression of MMP7 through the PI3K-AKT-mTOR signaling pathway.