Work

Mechanism of matrine inhibiting MRE11 lactylation and DNA damage repair in regulating cholangiocarcinoma sensitivity to I125 radiotherapy

Year: 2026

Type: article

Abstract: To investigate the mechanism by which matrine enhances the sensitivity of cholangiocarcinoma to I-125 radiotherapy through inhibiting MRE11 lactylation modification and DNA damage repair. HuCC-T1 human cholangiocarcinoma cells were treated with matrine and/or I-125 irradiation. Cell viability was assessed using CCK-8 assay, and cell apoptosis was detected by flow cytometry. Western blot was performed to analyze the expression of apoptosis-related proteins (BAX, BCL2, cleaved caspase-3, and cleaved PARP). Immunofluorescence was used to detect MRE11 and γ-H2AX expression. A nude mouse xenograft model was established to validate the findings in vivo. Matrine inhibited the proliferation of HuCC-T1 cells and induced apoptosis in a dose- and time-dependent manner. The combination of matrine and I-125 irradiation significantly enhanced DNA damage compared with I-125 alone. Mechanistically, matrine suppressed MRE11 lactylation modification, thereby inhibiting DNA damage repair. The in vivo experiments confirmed that matrine enhanced the therapeutic efficacy of I-125 radiotherapy in cholangiocarcinoma xenografts. Matrine enhances the sensitivity of cholangiocarcinoma to I-125 radiotherapy by inhibiting MRE11 lactylation modification and DNA damage repair, suggesting its potential as a radiosensitizer for cholangiocarcinoma treatment.

Source: Journal of Radiation Research and Applied Sciences

DOI: 10.1016/j.jrras.2026.102336

Authors: Linfang Xu, Jialing Li, Xing Li, Min Gong, Guiliang Wang

Institution: Jiangxi Pingxiang People's Hospital

Language: English

Topic: Cholangiocarcinoma and Gallbladder Cancer Studies

Subfield: Surgery

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $1,400