Yulangsan polysaccharide inhibits epithelial-mesenchymal transition and invasion in NSCLC by attenuating the TGF-β1/ERK signaling pathway

Am J Cancer Res. 2023 Aug 15;13(8):3401-3416. eCollection 2023.

Abstract

Active polysaccharides have unique advantages in inhibiting cancer cell proliferation, invasion and metastasis and inducing apoptosis. Yulangsan polysaccharide (YLSPS) is derived from the root of Millettia pulchra var. laxior (Dunn) Z. Wei. Previous studies revealed that YLSPS exhibits bioactivities such as antibacterial, antidepressive, antitumor, hepatoprotective and immunomodulating activities. However, the anticancer effects of YLSPS on lung cancer have not yet been studied, and its mechanism of action remains unclear. The present study investigated the anti-migration/invasion effects of YLSPS and possible mechanisms in lung cancer cells (A549 and Lewis) in vitro and in vivo. The data suggested that YLSPS reversed epithelial-mesenchymal transition (EMT) and inhibited the invasion and migration of lung cancer cells by inhibiting the TGF-β1-induced ERK signaling pathway. Furthermore, YLSPS reduced the levels of proteins associated with EMT, including vimentin, but increased those of E-cadherin, as determined by Western blotting. In vivo, YLSPS significantly inhibited the growth of xenograft tumors, and decreased the levels of TGF-β1 and protein markers associated with EMT. Importantly, YLSPS had fewer toxic side effects than cisplatin. Overall, YLSPS significantly delayed non-small cell lung cancer (NSCLC) progression by modulating EMT and TGF-β1/ERK signaling pathway. The present findings suggest that YLSPS may be a potential adjuvant therapy and drug for improving the tumor microenvironment of lung cancer.

Keywords: NSCLC; TGF-β1/ERK; Yulangsan polysaccharide; epithelial-mesenchymal transition; invasion; migration.