Astragaloside IV alleviates cisplatin-induced nephrotoxicity in Lewis lung carcinoma mice and inhibits the epithelial-mesenchymal transition-mediated invasion and metastasis of lung cancer cells

Abstract

Background: the high incidence of nephrotoxicity is a major limiting factor for the clinical use of cisplatin (CDDP), which affects severely the efficacy of chemotherapy. Astragaloside IV (AS-IV) is the characteristic monomer component of Astragalus membranaceus with prominent medical value in fibrosis, inflammation, autoimmune and cardiovascular diseases. However, whether AS-IV is feasible in combination with CDDP to alleviate the nephrotoxicity and the role of AS-IV in preventing the malignant transformation of tumor cells, have not been fully elucidated.Methods and results: this experiment established Lewis lung cancer mouse model through in vivo experiment. From the characteristics of mouse tumor and hematoxylin and eosin (H&E) staining and immunohistochemistry (IHC) analysis, kits, TUNEL and other experiments, it was proved that AS-IV could alleviate CDDP-induced nephrotoxicity through activating Nrf2 signaling to reduce the apoptosis of renal tubular epithelial cells and sensitize CDDP to enhance the inhibitory effect of Lewis lung carcinoma.In vitro, through Western blot, Wound healing assay and Transwell assays, we found that AS-IV could inhibit the invasion and metastasis ability of A549 cells via reversing the TNF-α and TGF-β co-stimulated epithelial-mesenchymal transition (EMT) process and down-regulated the expression of NF-κB(p65) synergistically. Conclusion: To sum up, the results of this study show that astragaloside IV reduces the nephrotoxicity of cisplatin induced Lewis lung cancer mice and inhibits the invasion and metastasis of lung cancer cells mediated by epithelial mesenchymal transformation.