[摘 要] 目的：探究甘氨胆酸（GCA）对肺腺癌A549细胞移植瘤小鼠放射治疗敏感性的影响及其机制。方法：建立A549人 肺腺癌细胞裸鼠移植瘤模型，随机分为移植瘤对照组（对照组）、GCA组、放疗组（RT组）和GCA + 放疗组（GCA + RT组）。RT组 和GCA + RT组接受单次10 Gy照射，GCA组及GCA + RT组连续7 d每日灌胃GCA 280 mg/kg。间隔2 d测量1次移植瘤体积， 末次给药后处死小鼠并取移植瘤组织，检测移植瘤组织中超氧化物歧化酶（SOD）与谷胱甘肽过氧化物酶（GSH-Px）活性，qPCR 法和WB法分别检测放疗关键基因（MCM6、ITGA6、CASP3等）mRNA和蛋白表达水平，H-E染色观察移植瘤组织的形态变化。 通过GEO（GSE276500、GSE294906、GSE218171）及TCGA数据库数据验证放疗关键基因。结果：GCA单用对瘤体生长有一定 抑制作用，但联合放疗的GCA + RT组相比单纯放疗组表现出放疗抵抗的效应（P < 0.05）。GCA 处理显著提高移植瘤组织 SOD活性（P < 0.01）、降低GSH-Px活性（P < 0.01），提示GCA可改变移植瘤抗氧化酶平衡，减弱放疗诱导的氧化应激。GCA干预 上调移植瘤组织中MCM6与ITGA6 mRNA表达、下调CASP3 mRNA表达（均P < 0.05）。GCA + RT组移植瘤组织中的MCM6蛋 白表达显著高于对照组（P < 0.05）。H-E染色显示，GCA组部分瘤组织坏死，而GCA + RT组坏死组织面积较RT组有所缩小。 GEO 和 TCGA 数据库验证支持 MCM6、ITGA6 高表达与放疗抵抗和预后不良相关。结论：GCA 通过增强 SOD 活性、降低 GSH-Px活性并上调ITGA6、MCM6的表达改变氧化应激与关键信号网络，从而削弱A549移植瘤对放疗的敏感性。

[Abstract] Objective: To investigate the effects and mechanisms of glycocholic acid (GCA) on the radiosensitivity of mice with lung adenocarcinoma A549 cell transplantation tumors. Methods: A lung adenocarcinoma A549 cell xenograft nude mouse model was established and randomized into four groups: the transplanted tumor control group (the control group), the GCA group, the radiotherapy (RT) group, and the GCA + RT group. The RT group and the GCA + RT group received a single 10 Gy irradiation; the GCA group and the GCA + RT group were gavaged with GCA at 280 mg/kg once daily for 7 consecutive days. Tumor volumes were monitored with two days between two measurements. After the last treatment mice were sacrificed and transplanted tumor tissues were collected. Superoxide dismutase (SOD) and glutathione peroxidase (GSH-Px) activities in transplantation tumor tissues were detected. qPCR and Western blot (WB) were used to detect the mRNA and protein expression levels of key radiation-related genes (MCM6, ITGA6, CASP3, etc.) respectively. Histomorphology was examined by H-E staining. External validation of candidate genes was performed using GEO datasets (GSE276500, GSE294906, and GSE218171) and TCGA. Results: GCA alone showed modest inhibition effect on tumor growth, whereas the GCA + RT group with combined radioactive therapy exhibited reduced radiosensitivity compared to the RT group with RT alone (P < 0.05). GCA treatment significantly increased SOD activity (P < 0.01) and decreased GSH-Px activity (P < 0.01) in transplanted tumor tissues, indicating that GCA might change antioxidant enzyme balance and reduce radiation-induced oxidative stress in transplanted tumors. GCA interference upregulated the mRNA expressions of MCM6 and ITGA6 and downregulated the mRNA expression of CASP3 in transplanted tumors (all P < 0.05). The expression of MCM6 protein was significantly higher in the transplanted tumor tissues of the GCA + RT group than that of the control group (P < 0.05). H-E staining showed partial tumor necrosis in the GCA group, while the necrotic area in the GCA + RT group grew smaller than that in the RT group. GEO and TCGA database analyses supported the association of high MCM6/ITGA6 expressions with radioresistance and poorer prognosis. Conclusion: GCA reduces the radiosensitivity of A549 xenografts by changing oxidative stress and key signaling network, such as enhancing SOD, lowering GSH-Px, and upregulating ITGA6 or MCM6.

[基金项目] 呼和浩特市卫生健康科技计划基金（2024-呼卫科-012）；内蒙古医学科学院公立医院科研联合基金科技项目 （2025GLLH0016）