@article{TRO5298,
author = {Fred Yi-Shueh Chen and Chih-Wen Chi and Hui-Ru Shieh and Chin-Ping Lin and Chun-Chuan Ko and Yi-Chun Chung and Jerry Chen-Yen Lai and Hung-Chi Tai and Yu-Jen Chen},
title = {Mitomycin C modulates tumor microenvironment and enhances radiosensitivity in rectal cancer},
journal = {Therapeutic Radiology and Oncology},
volume = {3},
number = {0},
year = {2019},
keywords = {},
abstract = {Background: Neoadjuvant chemoradiation is the standard of care for locally advanced rectal cancer, however, pathological complete response (pCR) rate remains unsatisfactory. Tumor hypoxia in rectal cancer might be one factor of radioresistance. Mitomycin C (MMC), a hypoxia-activated prodrug (HAP), enhances radiosensitivity and is the standard adjunct to radiotherapy (RT) in anal cancer. Our study evaluated the effect of MMC and RT on rectal cancer and its tumor microenvironment (TME).
Methods: In vitro hypoxia was induced by 1% O2 culture for CT26 rectal adenocarcinoma cells and HIF-1α expression was validated with Western blotting. Clonogenicity and MTT assays were used for radiation and drug survival. In syngeneic CT26 model, tumors were treated as follows: control, MMC (2 mg/kg/day), RT (2 Gy × 2 fractions), and combination with MMC 2 h prior to RT. Tumor volume, body weight, and white blood cell count were monitored for 1 month. Immune cells in TME were analyzed using flow cytometry.
Results: MMC inhibited cell viability and enhanced radioresponse in CT 26 cells with delayed repair of DNA double strand break (P},
issn = {2616-2768}, url = {https://tro.amegroups.org/article/view/5298}
}