关键词: 乳腺癌, 硝呋齐特, 奥拉帕尼, 同源重组修复

Abstract: Background and purpose: Nifuroxazide is an oral nitrouracil antibiotic commonly used to treat colitis and diarrhea. Studies have also shown anti-tumor effects of nifuroxazide by inhibiting STAT3 phosphorylation. In the study, through drug screening, nifuroxazide was found to affect homologous recombination (HR) repair of cells. Therefore, the possibility of nifuroxazide combined with poly (ADP-ribose) polymerase (PARP) inhibitor olaparib controlling breast cell growth was further explored. Methods: The SEE-SAW system was used to screen the drugs that had obvious effect on HR repair. Then, the effect of the drug screened on HR was further verified by HR/non-homologous end joining (NHEJ) fluorescence reporting system. DNA damage marker γH2AX foci after drug treatment was detected by immunofluorescence staining. Finally, MTS and clone formation assay were used to detect the effect of drug on cell proliferation. Results: Among 240 small molecule inhibitors screened, a STAT3 inhibitor, nifuroxazide, was found to significantly reduce the level of HR repair. Meanwhile, the combination of nifuroxazide and olaparib aggravated DNA damage and attenuated the ability of DNA damage repair in breast cancer cells. In addition, the combination of nifuroxazide and olaparib further enhanced the killing effect of olaparib on cancer cells. Conclusion: Nifuroxazide can increase the sensitivity of olaparib to breast cancer cells, and can be used as a potential sensitization drug for further study.

Key words: Breast cancer, Nifuroxazide, Olaparib, Homologous recombination repair