Mechanism and Synergistic Inhibition of of Yiqi Jianpi Huayu Recipe and 5-Fu on Gastric Cancer Lung Metastasis

OBJECTIVE To study the synergistic therapeutic effect of Yiqi Jianpi Huayu Recipe and 5-Fu on lung metastasis of gastric cancer in mice， and to elucidate the mechanism of tumor-associated macrophages (TAMs). METHODS 615 type mice were randomly divided into control group， model group， 5-Fu group， Yiqi Jianpi Huayu Recipe (YQJPHY) group， 5-Fu+ Yiqi Jianpi Huayu Recipe (5-Fu+YQJPHY) group. Except the control group， MFC cells were injected into the tail vein of each group to establish a mouse lung cancer metastasis model. After 2 weeks of administration， the tumor infiltrating lung tissues were observed， the lung metastasis inhibitory rates were calculated， TAMs and M1 and M2 ratios were determined by FCM， M2 expression was observed by immunohistochemistry， N-cadherin， snail and slug expression were detected by qPCR and Western blot. RESULTS In 5-Fu+YQJPHY group， the nodules and tumor infiltration were the least， and the inhibition rate was the highest (68.42%)， which was significantly higher than that in the other groups (P<0.05). Compared with 5-Fu group， the expression of M1 significantly increased， the expression of M2 significantly decreased， the expression of CD206 was weaker (P<0.05). The expression of N-cadharin， snail and slug in 5-Fu+YQJPHY group was significantly lower than 5-Fu group (P<0.05). CONCLUSION Yiqi Jianpi Huayu Recipe combined with 5-Fu shows obvious synergistic effect on inhibiting lung metastasis of gastric cancer in mice. The mechanism may be related to the induction of M2-type TAMs to M1-type transformation， thereby inhibiting EMT of tumor cells.