Mobile website
Basic Research
Effects and mechanisms of glycocholic acid on the radiosensitivity of mice with lung adenocarcinoma transplantation tumors
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
[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.
Keywords:
Project Supported:
Clc Number:
