Action Mechanism of Fuzheng Fangai Pill Combined with Cyclophosphamide on Tumor Metastasis and Growth

Fuzheng Fangai pill (FZFA), a traditional Chinese formula, is widely used for cancer treatment. Compared with other anticancer drugs, it is characterized by moderate and persistent efficacy with few side effects. The present paper emphasizes antitumor effect of FZFA combined with cyclophosphamide (CTX) on C57BL/6 mice subcutaneously injected with Lewis lung cancer cells, Comparing it with that of CTX. On the 21st day, a set of biochemical parameters were studied: the tumor weight and tumor volume, the inhibition rate of lung metastasis, the percentage and ratio of spleen CD4(+)IL-17(+) Th17 (T helper cell 17, Th17 for short) and CD4(+)CD25(+)Foxp3(+) Treg (T regulatory cell, Treg for short) cells, and the concentrations of IL-6, TGF-β, IL-17, IL-23, and IFN-γ in culture supernatants of CD4(+) T lymphocytes were determined. The expression of the splenic Foxp3 and RORγt mRNA and JAK2, STAT3, and SOCS3 protein as also determined. The results show that compared with the model control group and CTX group, FZFA+CTX restored the ratio of spleen CD4(+)IL-17(+) Th17 and CD4(+)CD25(+) Foxp3(+) Treg cells, and inhibited the inflammatory response including the nuclear SOCS3/JAK-STAT pathway, regulation of interleukins TGF-β, IL-6, IL-17, IL-23, and IFN-γ, and Foxp3 and RORγt gene expression in CD4(+) T lymphocytes. We conclude that FZFA+CTX strongly reduced the growth and metastasis rate of Lewis lung cancer through inhibition of SOCS/JAK-STAT pathway and inflammatory cytokine responses. FZFA + CTX had greater activity than CTX alone.