Authors
Wei Zhao, Qin Chen, Cuiping Yang, Yifan Chu, Jiyu Yang, Junru Chen, Dengyu Chen
Published in
European journal of pharmacology. Pages 179240. Aug 18, 2026. Epub Aug 18, 2026.
Abstract
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).
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.
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.
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.
PMID:
42612770
Bibliographic data and abstract were imported from PubMed on 19 Aug 2026.
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