Screening and anti-colorectal activity of small molecule inhibitors of Fusobacterium nucleatum
10.12206/j.issn.2097-2024.202405009
- VernacularTitle:具核梭杆菌小分子抑制剂的筛选及其抗结直肠癌活性研究
- Author:
Xuexin BAI
1
;
Yuping CHEN
1
;
Chunquan SHENG
1
;
Shanchao WU
1
Author Information
1. Department of Medicinal Chemistry, School of Pharmacy, Naval Medical University, Shanghai 200433, China.
- Publication Type:Originalarticles
- Keywords:
Fusobacterium nucleatum;
phenotypic screening;
anti-CRC;
organoids;
methotrexate
- From:
Journal of Pharmaceutical Practice and Service
2024;42(12):503-507
- CountryChina
- Language:Chinese
-
Abstract:
Objective To screen small molecule inhibitors of Fusobacterium nucleatum （Fn） based on commercially available compound libraries, and investigate their anti-colorectal cancer activities under Fn intervention in order to obtain novel anti-colorectal cancer lead compounds. Methods The promotion of colorectal cancer proliferation on organoid was validated by Fn. Secondly, the effects of anti-Fn compounds on their in vitro anticancer activity under Fn’s co-incubation with colorectal cancer HCT116 cell were comparative investigated. Finally, in vivo anticancer efficacy of highly active compounds on nude mouse colon cancer HCT116 transplanted tumor under the intervention of Fn was evaluated by gavage. Results Fn could significantly promote the proliferation of rectal cancer organoids. 9 anti-Fn active compounds could significantly enhance their in vitro anticancer activity under Fn’s co-incubation with HCT116 cells. Methotrexate had the strongest anti-cancer activity with IC50 as 0.03 μmol/L. The combined use of methotrexate (0.5 mg/kg) and PD-1 (5.0 mg/kg) had a stronger anti-tumor effect than their standalone use. Conclusion As new small molecule inhibitor of Fn, methotrexate exhibited good in vitro and in vivo anti-colorectal cancer activity against HCT116 cells and nude mouse xenografts under Fn intervention, which showed the foundation for subsequent structural optimization, and could be expected to expand the new indications of methotrexate.
