The anti-cancer effect of E. coli in coordination with sorafenib

Abstract

Objective To explore a new anticancer strategy by combination of E. coli and sorafenib in a rat Walker 256 tumor model. Methods Walker 256 cells (rat breast carcinoma cell line) were inoculated in liver of Wistar rats to establish an ectopic tumor model. Then intratumoral injection of E. coli 43013, which is tropic for tumor tissue other than normal tissue, was combined with or without sorafenib to treat the ectopic tumor. E. coli 43013 showed robust anticancer effects with the tumor volume decreased drastically and extensive necrosis and severe inflammation in peritumor tissue. Results E. coli 43013 in coordination with sorafenib have a better anticancer effects with smaller tumor volume and lower level of inflammation (P=0.015). Pathology analysis shows residual cancer absolutely disapears in coordination group when the E. coli group exist 40% of residual cancer rate. This therapy was safe according to blood cultures and gram stain assay. Immunostaining results showed that tumor cells underwent epithelial to mesenchymal transition (EMT) with epithelial marker cytokeratin (CK) upregulated and vascular endothelial growth factor (VEGF), Vimentin, matrix metalloproteinase (MMP)-9 and proliferating cell nuclear antigen (PCNA) downregulated by inflammation followed by E. coli 43013 intratumoral injection. Further research showed sorafenib could inhibit the cancer progression mediated by inflammatory associated pathway, which may be induced by necrotic debris of tumor cells, and tumor associated inflammatory cells. Conclusion Our results provide a potent new strategy by combination of microbe and multikinase inhibitor sorafenib for cancer therapy in clinical cancer management. Key words: E. coli; Sorafenib; Carcinoma, hepatocellular; Targeted therapy