Tumor-promoting effects of insulin-like growth factor 2 on gastric cancer by mediating Treg immunocompetence in rats

HU Lingli

doi:10.13431/j.cnki.immunol.j.20240061

Abstract：To investigate the promoting effect of insulin-like growth factor 2(IGF-2)on cancer by mediating Treg immune activity in rats with gastric cancer,total of 40 healthy male SD rats were selected and subcutaneously inoculated with gastric cancer SGC-7901 cell line in the right axilla to establish a gastric cancer model.The model rats were randomly divided into a model group,a low-dose group(25 μg/kg IGF-2),a medium dose group(50 μg/kg IGF-2)and a high-dose group(100 μg/kg IGF-2),with 10 rats in each group.After continuous 14 days of administration,the tumor volume,tumor mass,thymus and spleen weight of rats in the 4 groups were observed and recorded for calculate tumor inhibition rate,thymus index and spleen index.Furthermore,Treg and Th17 levels in blood were detected by flow cytometry,tumor histopathological morphology was observed by hematoxylin-eosin staining,the apoptosis of gastric cancer cells was detected by TUNEL,and the expression of PI3K/Akt signaling pathway in tumor tissues of rats in 4 groups were detected by Western blotting.Data showed that the spleen index and thymus index of each dose group were lower than those of the model group,and showed a significant decreasing trend with the increase of the dosage,while the tumor promotion rate showed an increasing trend(P<0.05).Compared with the model group,IGF inhibited the apoptosis rate of cancer cells in each dose group in a dose-dependent manner(P<0.05).With the increase of IGF-2 dose,Treg,Th17 and Treg/Th17 all increased significantly(P<0.05)in IGF groups.The expression levels of p-Akt and CYP19A1 proteins in different dose groups were higher than those in the model group.As the dosage increased,the expression levels of p-Akt and CYP19A1 proteins showed a significant increase trend(P<0.05).Taken together,IGF-2 can promote tumor growth in gastric cancer rats,and its mechanism may relate to disrupting the immune function balance of Treg/Th17 cells through up-regulation of PI3K/Akt signaling pathway,thus inhibiting tumor cell apoptosis.