European journal of pharmacology · 2026
Attenuated Salmonella typhimurium L-forms combined with lentiviral shRNA-HOTAIR suppress tumorigenicity and aggressiveness of murine breast cancer by inhibiting EGFR/Snail/MMP9 pathway.
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Tang Ziqing, Zhao Wei, Yang Cuiping, Chen Qin, Yao Wenhui, Zhang Yunjie, Chu Yifan, Yang Jiyu, Chen Junru, Chen Dengyu
Аннотация
UNLABELLED: Breast cancer is a leading malignancy in women. HOTAIR promotes tumor proliferation, invasion, and EMT. This study evaluated combined therapy of attenuated Salmonella typhimurium (ST) L-forms and lentiviral shRNA-HOTAIR on triple-negative breast cancer in a murine model.
METHODOLOGY: ST VNP20009 L-forms were induced by ceftriaxone. 4T1 cell invasion was assessed by Transwell Matrigel assay and apoptosis by Annexin V/PI flow cytometry in vitro and TUNEL in vivo. Tumorigenicity and aggressiveness were evaluated in a mouse breast cancer model. EGFR, Snail, and MMP9 expression in xenografts was detected by RT-qPCR and immunohistochemistry.
RESULTS: ST L-forms appeared as Gram-negative bacteria with irregular red staining and long filament bodies. Transwell invasion assay showed attenuated ST and its L-forms inhibited 4T1 cell invasion in vitro. Annexin V/PI and TUNEL assays revealed that combining ST L-forms with lentiviral shHOTAIR induced significantly greater apoptosis in 4T1 cells compared to control, ST, or ST L-forms alone in vitro and in vivo. Furthermore, this combination more effectively suppressed tumor growth and aggressiveness in murine breast cancer. IHC and RT-qPCR on xenografts showed that the combination more effectively suppressed expression of EGFR, Snail, and MMP9 compared to controls.
CONCLUSION: This study confirmed that the combination of attenuated S. typhimurium L-forms and lentiviral shRNA-HOTAIR significantly enhanced the suppression of tumor growth and aggressiveness in murine breast cancer. These findings supported the potential of this combined strategy of attenuated ST L-forms and lentiviral shHOTAIR as a novel and more effective bio-therapeutic approach for bacterial-mediated breast cancer therapy.
METHODOLOGY: ST VNP20009 L-forms were induced by ceftriaxone. 4T1 cell invasion was assessed by Transwell Matrigel assay and apoptosis by Annexin V/PI flow cytometry in vitro and TUNEL in vivo. Tumorigenicity and aggressiveness were evaluated in a mouse breast cancer model. EGFR, Snail, and MMP9 expression in xenografts was detected by RT-qPCR and immunohistochemistry.
RESULTS: ST L-forms appeared as Gram-negative bacteria with irregular red staining and long filament bodies. Transwell invasion assay showed attenuated ST and its L-forms inhibited 4T1 cell invasion in vitro. Annexin V/PI and TUNEL assays revealed that combining ST L-forms with lentiviral shHOTAIR induced significantly greater apoptosis in 4T1 cells compared to control, ST, or ST L-forms alone in vitro and in vivo. Furthermore, this combination more effectively suppressed tumor growth and aggressiveness in murine breast cancer. IHC and RT-qPCR on xenografts showed that the combination more effectively suppressed expression of EGFR, Snail, and MMP9 compared to controls.
CONCLUSION: This study confirmed that the combination of attenuated S. typhimurium L-forms and lentiviral shRNA-HOTAIR significantly enhanced the suppression of tumor growth and aggressiveness in murine breast cancer. These findings supported the potential of this combined strategy of attenuated ST L-forms and lentiviral shHOTAIR as a novel and more effective bio-therapeutic approach for bacterial-mediated breast cancer therapy.