Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response

Yuying Ye; Mengting Lin; Guiyu Zhou; Weiyu Wang; Yinyin Yao; Yafei Su; Jianqiang Qi; Yanfang Zheng; Chunlian Zhong; Xi Chen; Mingqing Huang; Yusheng Lu

doi:10.3389/fphar.2024.1355650

Fuyuan decoction prevents nasopharyngeal carcinoma metastasis by inhibiting circulating tumor cells/ endothelial cells interplay and enhancing anti-cancer immune response

Front Pharmacol. 2024 Apr 25:15:1355650. doi: 10.3389/fphar.2024.1355650. eCollection 2024.

Authors

Yuying Ye^#¹, Mengting Lin^#^{2

3

4}, Guiyu Zhou^{3

4}, Weiyu Wang^{2

3

4}, Yinyin Yao^{2

3

4}, Yafei Su⁵, Jianqiang Qi⁶, Yanfang Zheng², Chunlian Zhong^{3

4}, Xi Chen¹, Mingqing Huang², Yusheng Lu^{3

4}

Affiliations

¹ Department of Otorhinolaryngology, Affiliated People's Hospital (Fujian Provincial People's Hospital), Fujian University of Traditional Chinese Medicine, Fuzhou, China.
² College of Pharmacy, Fujian Key Laboratory of Chinese Materia Medica, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
³ Fujian-Taiwan-Hongkong-Macao Science and Technology Cooperation Base of Intelligent Pharmaceutics, College of Material and Chemical Engineering, Minjiang University, Fuzhou, China.
⁴ Fuzhou Institute of Oceanography, Minjiang University, Fuzhou, China.
⁵ Department of Otorhinolaryngology, Fuzhou Second Hospital, Fuzhou, China.
⁶ Center for Teaching of Clinical Skills, Fujian University of Traditional Chinese Medicine, Fuzhou, China.

^# Contributed equally.

Abstract

Distant metastasis is a major cause of treatment failure in cancer patients and a key challenge to improving cancer care today. We hypothesized that enhancing anti-cancer immune response and inhibiting circulating tumor cells (CTCs) adhesion and transendothelial migration through synergistic multi-target approaches may effectively prevent cancer metastasis. "Fuyuan Decoction" (FYD) is a traditional Chinese medicine compound that is widely used to prevent postoperative metastasis in cancer patients, but its underlying mechanism remains unclear. In this work, we systematically elucidated the underlying molecular mechanism by which FYD prevents cancer metastasis through multi-compound and multi-target synergies in vitro and in vivo. FYD significantly prevented cancer metastasis at non-cytotoxic concentrations by suppressing the adhesion of CTCs to endothelial cells and their subsequent transendothelial migration, as well as enhancing anti-cancer immune response. Mechanistically, FYD interrupts adhesion of CTCs to vascular endothelium by inhibiting TNF-α-induced CAMs expression via regulation of the NF-κB signaling pathway in endothelial cells. FYD inhibits invasion and migration of CTCs by suppressing EMT, PI3K/AKT and FAK signaling pathways. Moreover, FYD enhances the anti-cancer immune response by significantly increasing the population of Tc and NK cells in the peripheral immune system. In addition, the chemical composition of FYD was determined by UPLC-HRMS, and the results indicated that multiple compounds in FYD prevents cancer metastasis through multi-target synergistic treatment. This study provides a modern medical basis for the application of FYD in the prevention of cancer metastasis, and suggesting that multi-drug and multi-target synergistic therapy may be one of the most effective ways to prevent cancer metastasis.

Keywords: Fuyuan decoction; anti-cancer immune response; cancer metastasis prevention; cell adhesion; traditional Chinese medicine; transendothelial migration.

Grants and funding

The author(s) declare financial support was received for the research, authorship, and/or publication of this article. This research was supported by the National Natural Science Foundation of China (NSFC, grant numbers 81703555, 81973437, and 82274080), the Department of Science and Technology of Fujian Province (grant numbers 2020J01859, 2021J011037, 2021D043, and 2022J01850), the Fujian Provincial Health Commission (grant numbers 2021QNA055), the Fujian Provincial Marine Economic Development Special Fund Project (FJHJF-L-2021-4), the Collaborative Innovation Platform Project of Fuxiaquan National Innovation Demonstration Zone (2021FX02), the Science and Technology Planning Projects of Fuzhou, China (grant number 2021S094), the Science and Technology Planning Projects of Fuzhou Institute of Oceanography, China (grant number 2021F08), the Young and Middle-aged Teacher Education Research Project of Fujian Province (grant number JAT210141).