Preliminary study on synergistic effect of nifuroxazide and olaparib on growth inhibition in breast cancer cells

侯　净; 程纪淦; 王　华; 魏　娜; 倪　青

doi:10.19401/j.cnki.1007-3639.2021.12.004

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Preliminary study on synergistic effect of nifuroxazide and olaparib on growth inhibition in breast cancer cells

更新时间：2025-12-31

- Preliminary study on synergistic effect of nifuroxazide and olaparib on growth inhibition in breast cancer cells
- China Oncology Vol. 31, Issue 12, Pages: 1168-1173(2021)
- 作者机构：
  
  贵州省人民医院乳腺外科,贵州,贵阳,550002
- 作者简介：
- 基金信息：
- DOI：10.19401/j.cnki.1007-3639.2021.12.004
  CLC：
- Published Online：07 January 2022，
  
  Published：07 January 2021
- 稿件说明：
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侯　净, 程纪淦, 王　华, 魏　娜, 倪　青. 硝呋齐特增加乳腺癌细胞对奥拉帕利敏感性的初步研究[J]. 中国癌症杂志, 2021, 31(12): 1168-1173.

侯　净, 程纪淦, 王　华, et al. Preliminary study on synergistic effect of nifuroxazide and olaparib on growth inhibition in breast cancer cells[J]. China Oncology, 2021, 31(12): 1168-1173.
侯　净, 程纪淦, 王　华, 魏　娜, 倪　青. 硝呋齐特增加乳腺癌细胞对奥拉帕利敏感性的初步研究[J]. 中国癌症杂志, 2021, 31(12): 1168-1173. DOI： 10.19401/j.cnki.1007-3639.2021.12.004.

侯　净, 程纪淦, 王　华, et al. Preliminary study on synergistic effect of nifuroxazide and olaparib on growth inhibition in breast cancer cells[J]. China Oncology, 2021, 31(12): 1168-1173. DOI： 10.19401/j.cnki.1007-3639.2021.12.004.

摘要

背景与目的：硝呋齐特（nifuroxazide）是一种口服硝基呋喃类抗生素，常用于治疗结肠炎和腹泻，硝呋齐特可抑制STAT3磷酸化而发挥抗肿瘤作用。通过药物筛选发现硝呋齐特能影响细胞DNA同源重组（homologous recombination，HR）修复，进一步对硝呋齐特与聚腺苷二磷酸核糖聚合酶［poly (ADP-ribose) polymerase，PARP］抑制剂奥拉帕利（olaparib）联合应用的可能性进行初步探索。方法：采用See-Saw系统筛选对细胞DNA HR修复影响明显的药物，然后用HR/非同源末端连接（non-homologous end joining，NHEJ）荧光报告系统进一步验证筛选药物对HR的影响。采用免疫荧光染色技术检测药物处理后DNA损伤标记γH2AX焦点形成情况。最后用MTS及克隆形成实验检测药物处理后对细胞增殖的影响。结果：通过筛选240个小分子抑制剂发现，STAT3抑制剂硝呋齐特可显著降低细胞HR修复水平。硝呋齐特与奥拉帕利联用可增加乳腺癌细胞DNA损伤程度并降低DNA损伤修复能力。此外，硝呋齐特与奥拉帕利联用可进一步提高奥拉帕利对癌细胞的杀伤作用。结论：硝呋齐特能增加乳腺癌细胞对奥拉帕利的敏感性，可作为奥拉帕利潜在增敏药物，值得进一步研究。

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.

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Department of Breast Surgery, National Cancer Center/National Clinical Research Center for Cancer/Cancer Hospital, Chinese Academy of Medical Sciences and Peking Union Medical College

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