Designing Dihydrofolate Reductase Inhibitors as X-ray Radiosensitizers to Reverse Radioresistance of Cervical Cancer.

ABSTRACT: X-ray radiotherapy has been widely used in the treatment of cervical cancer, a common gynecologic malignant tumor. However, the therapeutic efficacy tends to be indistinctive. One major reason for this is amplification of the dihydrofolate reductase (DHFR) gene, which causes an increase in DHFR activity and attenuation of the treatment effect. To solve this problem, we synthesized a series of DHFR inhibitors derived from methotrexate (MTX) analogues as radiotherapy sensitizers. Activity screening revealed that compound 2a exerted the best inhibitory effect toward DHFR activity. In combination with X-ray radiotherapy (4 Gy), 2a showed much more prominent antiproliferative activity on cervical cancer cells than 2a or X-rays alone and revealed higher selectivity and radio

SUBMITTER: Liang Y 

PROVIDER: S-EPMC7357216 | biostudies-literature | 2020 Jul

REPOSITORIES: biostudies-literature