Attenuated Salmonella typhimurium VNP20009 L-forms suppress tumor growth and metastasis by inhibiting TGF-β1/Snail/Vimentin pathway in murine lung cancer.

BACKGROUND: Attenuated Salmonella typhimurium (ST) VNP20009 exhibits tumor-targeting properties but limited therapeutic efficacy. Bacterial L-forms, which lack a cell wall, may offer enhanced antitumor activity. This study compared the efficacy of VNP20009 and its bacterial L-forms against murine Lewis lung carcinoma (LLC) and investigated the underlying mechanisms involving apoptosis and epithelial-mesenchymal transition (EMT). METHODS: The effects of attenuated ST VNP20009 and its L-forms on LLC cell invasion and apoptosis were assessed in vitro. C57BL/6 mice bearing subcutaneous LLC tumors or experimental lung metastases were treated with intratumoral or intravenous bacterial therapy. Tumor growth, metastatic nodules, apoptosis, and the expressions of TGF-β1, Snail, and Vimentin were evaluated. RESULTS: Attenuated ST VNP20009 L-forms demonstrated superior inhibition of LLC cell invasion and induction of apoptosis in vitro, compared to the parental strain. In vivo, attenuated ST VNP20009 L-forms significantly suppressed subcutaneous tumor growth and reduced pulmonary metastasis, compared to ST VNP20009 treatment group. Meanwhile, the ST L-forms treatment group exhibited more apoptosis and more downregulation of TGF-β1, Snail, and Vimentin at both protein and mRNA levels. CONCLUSION: Attenuated ST L-forms can effectively inhibit tumor growth and metastasis in mouse lung cancer by inducing apoptosis and suppressing TGF-β1/Snail/Vimentin pathway. Our study represented a promising application strategy for improving the therapeutic efficacy of bacterial-mediated tumor therapy by using attenuated S. typhimurium VNP20009 L-forms.