Astragali Radix-Curcumae Rhizoma Regulates Th17/Treg Cell Balance in the Mouse Model of Lewis Lung Carcinoma via C5a-Mediated JAK2/STAT3 Pathway
Objective To study the regulatory effect of Astragali Radix-Curcumae Rhizoma(AR-CR)on Th17/Treg cell balance in the tumor microenvironment by regulating the C5a-mediated Janus kinase 2(JAK2)/signal transducer and activator of transcription 3(STAT3)pathway,thereby deciphering the mechanism of this herb pair in inhibi-ting tumor progression.Methods Forty male C57BL/6 mice were assigned by the random number table method into blank control,model control,AR-CR,and positive control(PMX53)groups,with 10 mice in each group.Lewis cells were inocu-lated in the armpit to establish a mouse model of lung cancer.From day 3 after inoculation,the mice in the AR-CR group were administrated with the decoction of AR-CR at a dose of 8.2 g/kg by gavage,and those in the model control and PMX53 groups were administrated with the equal volume of sterilized double-distilled water by gavage for 14 consecutive days.The PMX53 group was subjected to intraperitoneal injection of PMX53 at a dose of 1 mg/kg on days 3,6,9,12,and 15,respectively,and the model control and AR-CR groups were injected intraperitoneally with equal-volume PBS solu-tion at the same time.The tumor volume of each group was measured every 2 days and the tumor growth curve was drawn.All the mice were executed on day 15,and the tumor mass was collected.The serum levels of C5 a,interleukin(IL)-6,IL-10,IL-17,and transforming growth factor(TGF)-β were determined by ELISA.The proportion of Th17/Treg cells in the peripheral blood and tumor tissue was examined by flow cytometry and calculated.The protein and mRNA levels of JAK2/STAT3 signaling pathway-related factors were determined by Western blotting and real-time PC R,respectively.Results Compared with the model control group,the AR-CR and PMX53 groups showed slow tumor growth,down-reg-ulated mRNA and protein levels of C5a,JAK2,and STAT3,decreased p-JAK2/JAK2 and p-STAT3/STAT3 ratios,re-duced proportion of Treg cells,up-regulated protein and mRNA levels of SOCS3,and increased Th17/Treg ratio(all P＜0.05).Conclusion AR-CR can reduce complement C5a to inhibit the activation of JAK2/STAT3 pathway and regulate the Th17/Treg cell balance,thereby inhibiting tumor growth.
NETL
NSTL
万方数据
