Notoginsenoside Ft1 inhibits colorectal cancer growth by increasing CD8⁺ T cell proportion in tumor-bearing mice through the USP9X signaling pathway

Abstract

The management of colorectal cancer (CRC) poses a significant challenge, necessitating the development of innovative and effective therapeutics. Our research has shown that notoginsenoside Ft1 (Ng-Ft1), a small molecule, markedly inhibits subcutaneous tumor formation in CRC and enhances the proportion of CD8⁺ T cells in tumor-bearing mice, thus restraining tumor growth. Investigation into the mechanism revealed that Ng-Ft1 selectively targets the deubiquitination enzyme USP9X, undermining its role in shielding β-catenin. This leads to a reduction in the expression of downstream effectors in the Wnt signaling pathway. These findings indicate that Ng-Ft1 could be a promising small-molecule treatment for CRC, working by blocking tumor progression via the Wnt signaling pathway and augmenting CD8⁺ T cell prevalence within the tumor environment.

Keywords

Notoginsenoside Ft1 / Colorectal cancer / CD8⁺ T cell / Ubiquitin-specific peptidase 9 X-linked / β-Catenin / Wnt

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Funding

Shanghai Pujiang Program(20PJ1413000)

National Natural Science Foundation of China(82173106)

National Natural Science Foundation of China(82130115)

National Natural Science Foundation of China(81290108033)

National Natural Science Foundation of China(82004004)

National Natural Science Foundation of China(82074011)