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

Yutao Feng; Yuan Li; Fen Ma; Enjiang Wu; Zewei Cheng; Shiling Zhou; Zhengtao Wang; Li Yang; Xun Sun; Jiwei Zhang

doi:10.1016/S1875-5364(24)60623-0

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

Chin J Nat Med. 2024 Apr;22(4):329-340. doi: 10.1016/S1875-5364(24)60623-0.

Authors

Yutao Feng¹, Yuan Li¹, Fen Ma¹, Enjiang Wu¹, Zewei Cheng¹, Shiling Zhou¹, Zhengtao Wang¹, Li Yang², Xun Sun³, Jiwei Zhang⁴

Affiliations

¹ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China.
² Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: yl7@shutcm.edu.cn.
³ Gastrointestinal surgery, Longhua Hospital, Shanghai University of Traditional Chinese Medicine, Shanghai 200032, China. Electronic address: shsunxun@sina.cn.
⁴ Shanghai Key Laboratory of Compound Chinese Medicines, The MOE Key Laboratory for Standardization of Chinese Medicines, Institute of Chinese Materia Medica, Shanghai University of Traditional Chinese Medicine, Shanghai 201203, China. Electronic address: joezhang@shutcm.edu.cn.

PMID: 38658096
DOI: 10.1016/S1875-5364(24)60623-0

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: CD8(+) T cell; Colorectal cancer; Notoginsenoside Ft1; Ubiquitin-specific peptidase 9 X-linked; Wnt; β-Catenin.

MeSH terms

Animals
CD8-Positive T-Lymphocytes* / drug effects
Cell Line, Tumor
Colorectal Neoplasms* / drug therapy
Colorectal Neoplasms* / metabolism
Ginsenosides / pharmacology
Ginsenosides / therapeutic use
Humans
Mice
Mice, Inbred BALB C
Signal Transduction / drug effects
Ubiquitin Thiolesterase* / genetics
Ubiquitin Thiolesterase* / metabolism
Wnt Signaling Pathway* / drug effects
beta Catenin / metabolism

Substances

Ubiquitin Thiolesterase
Ginsenosides
USP9X protein, human
beta Catenin