Observation On Inhibiting The Growth Of Xenografted Tca8113Tumors By Combination Of Tumor-targeting Salmonella And Chemotherapy

To evaluate the effect of tumor-targeting Salmonella typhimuriumVNP20009combined with cyclophosphamide (CTX) or pinyangmycin (PYM) on inhibiting the growth of xenografted Tca8113tumors on nude mice and its side effects, and to provide the theoretical basis for its clinical application in the treatment of oral squamous cell carcinoma (SCC). Methods:The xenografted Tca8113tumors were established by inoculating thehumans tongue SCC cell line Tca8113subcutaneously into the nude mice in SPF-laboratory. The mice were randomly divided into six groups, including VNP, VNP+CTX, VNP+PYM and CTX, PYM, blank groups as control. The growth of tumors was observed. At the7and14day,3 mice in each group were sacrificed randomly whose samples of blood, tumor and liver were collected. The bacteria titer in tumor and liver tissues was detected. The serum level of vascular endothelial growth factor (VEGF) was measured by ELISA assay, and the serum level of alanine transaminase (ALT) and aspartate transaminase (AST) was measured by automatic biochemical analyzer. The necrosis in the tumors was observed by hematoxylin and eosin (HE) staining, and microvessel density (MVD) in the tumors was investigated by immunohistochemistry staining for CD105. The degree of hepatic injury was observed by HE staining.Results:At the30th day, the tumor inhibitory rate of VNP group is32.92%; CTX group,17.44%; VNP+CTX group,61.72%; PYM group,47.23%; VNP+PYM group,79.92%respectively. Compared with chemotherapy alone or VNP alone, the tumor average volume of VNP+CTX group and VNP+PYM group decreased significantly (P<0.01). At the14th day, the level of serum VEGF and the tumor MVD of VNP+CTX group and VNP+PYM group were lower than chemotherapy alone or VNP alone. More severe necrosis was observed within tumors of VNP group, VNP+CTX group and VNP+PYM group than the other three groups under microscope (x100).At the7th day and14th day after injection of bacteria, the bacteria titer was no significant difference between VNP+CTX group and VNP group (P>0.05). The bacteria titer in tumor of PYM+VNP group was higher than VNP group at the7th day (P<0.05), but lower than VNP group at the14th day (P<0.05). The bacteria titer in liver of VNP+CTX group and VNP+PYM group were lower than VNP group at the7th day and14th day (P<0.05).The levels of serum ALT of VNP group were higher than the other5groups at the14th day (P<0.05), but the levels of serum ALT of VNP+CTX group and VNP+PYM group did not increase compared with the control groups (P>0.05). Lymphocyte infiltration and sporadic necrosis were observed in livers of VNP group under microscopy at the14th day. Some degeneration was observed in livers of VNP+CTX group. No degeneration or necrosis was observed in livers of the other4groups.Conclusion:It was revealed that Salmonella VNP20009with peritumoral injection could preferentially accumulate within xenografted Tca8113tumor and inhibit the tumor growth. Salmonella VNP20009combined with chemotherapy could reduce tumor angiogenesis and enhance the antitumor effect on xenografted Tca8113tumor. Chemotherapy could enhance the tumor-targeting of Salmonella VNP20009, but not increase the side effects. The combination of Salmonella VNP20009and chemotherapy may be a promising clinical treatment of oral SCC.