复方胃肠安调控肿瘤相关巨噬细胞铁死亡抑制胃癌的作用探讨OA

Objective To explore the mechanisms by which Compound Weichang'an Decoction inhibits gastric cancer by promoting tumor-associated macrophages(TAMs)ferroptosis.Methods Animal experiment:An orthotopic transplantation tumor model of human gastric cancer was established in nude mice.Fifteen female BALB/c nude mice were divided into a Compound Weichang'an group,a 5-fluorouracil(5-FU)group,and a model group by the random number table method,with five mice in each group.Cell experiment:The Compound Weichang'an Decoction group was administered Compound Weichang'an Decoction at 41.86 g/kg via gavage,the 5-FU group was administered 5-FU at 90 mg/kg via intraperitoneal injection,and the model group was administered an equivalent volume of normal saline.After 21 consecutive days of treatment,all mice were euthanized,and gastric tumors in primary lesions were harvested to calculate the tumor inhibition rate.Additionally,three healthy female BALB/c nude mice were used to prepare Compound Weichang'an Decoction-containing serum.THP-1 cells were induced by phorbol 12-myristate 13-acetate(PMA)to differentiate into M0 macrophages,serving as a TAMs model.Then,this model was divided into a Compound Weichang'an Decoction-containing serum group,a 5-FU group,and a control group.Cell viability of TAMs in each group was detected using the Cell Counting Kit-8(CCK-8)assay to identify the optimal concentration of Compound Weichang'an Decoction-containing serum.Subsequently,ferrous ion(Fe2+)content in TAMs was measured via ferrous ion colorimetry.The fluorescence signal of reactive oxygen species(ROS)in TAMs was detected using the 2',7'-dichlorodihydrofluorescein diacetate(DCFH-DA)fluorescent probe.Mitochondrial membrane potential was evaluated by flow cytometry and the JC-1 kit.Finally,Western blot was employed to determine the expression levels of ferroptosis-related proteins,including glutathione peroxidase 4(GPX4),solute carrier family 7 member 11(SLC7A11),and acyl-CoA synthetase long-chain family member 4(ACSL4).Results Animal experimental results showed that:Compound Weichang'an Decoction demonstrated an inhibition rate of 49％against gastric orthotopic transplantation tumors.Cell experimental results showed that:Compared with the control group,the Compound Weichang'an Decoction-containing serum groups at different concentrations exhibited reduced TAMs viability(P＜0.05,P＜0.01).Compound Weichang'an Decoction-containing serum group showed increased Fe2+and ROS content,decreased mitochondrial membrane potential(P＜0.05,P＜0.01),increased GPX4 and SLC7A11 protein expression levels(P＜0.01),and decreased ACSL4 protein expression levels(P＜0.01)in TAMs.Conclusion Compound Weichang'an Decoction can inhibit gastric cancer,with potential mechanisms related to promoting TAMs ferroptosis.