Attenuated Salmonella typhimurium L forms combined with lentivirus shRNA-HOTAIR effectively inhibit tumor growth and metastasis in murine epithelial ovarian cancer.

Epithelial ovarian cancer (EOC) is a common gynecological malignant tumor, with a high mortality rate. HOX antisense intergenic RNA (HOTAIR) in lncRNAs is involved in various tumor epithelial-mesenchymal transition (EMT) processes. For seeking better treatment strategies, we studied the effects of attenuated Salmonella typhimurium (ST) L forms combined with lentivirus shRNA-HOTAIR on in vivo tumorigenicity and metastasis of murine EOC cells, and the related anti-tumor mechanisms. Attenuated ST VNP20009 was induced into bacterial L forms by using ceftriaxone. ST L forms were appeared red in Gram staining. Attenuated ST L forms can inhibit the invasion ability of EOC cells in vitro. TUNEL assays showed that attenuated ST L forms combined with lentivirus shHOTAIR can induce more apoptosis of ID8 cells in murine ovarian tumors, compared to the negative control group and only ST or bacterial L forms therapy group. Meanwhile, attenuated ST L forms combined with lentivirus shHOTAIR more effectively inhibited tumor growth and lung metastasis in murine ovarian tumors. The tumorigenicity-related proteins of xenograft tumors detected by immunohistochemistry and qRT-PCR assays showed that attenuated ST L forms combined with lentivirus shHOTAIR can more effectively decrease the protein and mRNA expressions which promote tumor growth and metastasis, such as TGF-β1, ZEB1 and Vimentin. This study confirmed that attenuated ST L forms combined with lentivirus shHOTAIR can more effectively suppress tumor growth and lung metastasis in murine ovarian tumors. Attenuated ST L forms combined with lentivirus shHOTAIR may serve as a better novel biological strategy for bacterial-mediated tumor therapy in EOC.