Isoliquiritigenin alleviates radiation-induced intestinal injury in lung cancer by inhibiting TNF-α/caspase3 signaling pathway.

To construct a model of intestinal injury induced by radiotherapy for lung cancer and to study the protective effect and mechanism of isoliquiritigenin. The lungs of mice were irradiated with 0, 2, 4, 6, 8 Gy X-rays to screen the optimal radiation dose. A mouse model of lung cancer was established, and the tumor was irradiated once. At 3, 7, and 10 days after irradiation, H&E was used to detect the pathological manifestations of colon tissue in mice, and WB was used to detect the expression level of tight junction protein in colon tissue, so as to screen the best time point and study its possible mechanism. Molecular docking was used to study the tightness of isoliquiritigenin binding to TNF-α. Isoliquiritigenin (40 mg/kg) was given on the next day after 4 Gy X-ray irradiation. The levels of TNF-α and apoptosis, intestinal mucosal barrier function, MUC2 protein expression, and colon stem cell proliferation were detected. 4Gy X-ray local irradiation induced obvious colon injury in mice, and the injury was obvious on the 7th day. Isoliquiritigenin significantly improved the general condition, colonic histopathological changes, intestinal stem cell proliferation, and colonic tight junction function of lung cancer-bearing mice after radiotherapy. Further studies have found that isoliquiritigenin can downregulate the activation of TNF-α/Caspase-3 signaling pathway by inhibiting the expression of pro-inflammatory factor TNF-α, alleviate the apoptosis of colonic epithelial cells, improve the upregulation of colonic tight junction function, regulate the expression of MUC2, and promote the proliferation of intestinal stem cells, which may be related to the stable binding of isoliquiritigenin to TNF-α. Radiotherapy-induced bystander effect of lung cancer may be related to the abnormal expression of TNF-α. Isoliquiritigenin may downregulate the expression of TNF-α by binding to TNF-α, inhibit the apoptosis of colon cells, promote the proliferation of intestinal stem cells, and maintain the intestinal mucosal barrier to alleviate the colon injury induced by radiation bystander effect.