Tumor-targeting Salmonella typhimurium improves cyclophosphamide chemotherapy at maximum tolerated dose and low-dose metronomic regimens in a murine melanoma model.
Chemotherapy for cancer is partly limited by the inability of drugs to act on poorly vascularized or avascularized areas of tumors. Tumor-targeting bacteria are capable of preferentially replicating in these poorly perfused regions. Some strains have been combined with chemotherapeutic agents and the results have been promising. However, no systematic work has been carried out to test the effect of bacteria on clinical modes of chemotherapy, such as standard maximum tolerated dose (MTD) and novel low-dose metronomic (LDM) chemotherapy. Here Salmonella typhimurium VNP20009 was combined with cyclophosphamide (CTX) at both MTD and LDM schedules in a murine melanoma model. The results showed that VNP20009 significantly improved the effects of all forms of CTX treatments. The combination of VNP20009 and CTX led to a more significant decrease in tumor microvessel density and serum vascular endothelial growth factor (VEGF) level, compared with either treatment alone. Furthermore, combination therapy remarkably increased the number of bacteria within tumors when compared with bacteria treatment alone. These findings suggest that tumor-targeting bacteria, in conjunction with CTX at standard MTD and LDM regimens, might be of clinical value for the treatment of melanoma.
Jia
Li-Jun
LJ
State Key Laboratory of Pharmaceutical Biotechnology, Department of Biochemistry, College of Life Science, Nanjing University, Nanjing 210093, People's Republic of China.
Wei
Dong-Ping
DP
Sun
Qi-Ming
QM
Jin
Guang-Hui
GH
Li
Shu-Feng
SF
Huang
Yan
Y
Hua
Zi-Chun
ZC
D000818:Animals; D003131:Combined Modality Therapy; D003520:Cyclophosphamide / Q000008:administration & dosage*; D020714:Maximum Tolerated Dose; D008546:Melanoma, Experimental / Q000098:blood supply / Q000382:microbiology / Q000628:therapy*; D051379:Mice; D009389:Neovascularization, Pathologic; D012486:Salmonella typhimurium / Q000235:genetics / Q000254:growth & development; D013997:Time Factors; D042461:Vascular Endothelial Growth Factor A / Q000097:blood
D042461:Vascular Endothelial Growth Factor A; D003520:Cyclophosphamide