Synergistic antitumor effects of 5-fluorouracil and vorinostat in preclinical models of pheochromocytomas and paragangliomas.

Authors

Wenqian Zhang, Yue Zhou, Yunying Cui, Tianyi Li, Zewen Li, Weidong Ren, Anli Tong

Published in

Endocrine. Volume 91. Issue 1. Oct 10, 2026. Epub Oct 10, 2026.

Abstract

Therapeutic options for metastatic pheochromocytomas and paragangliomas (PPGLs) are largely limited, highlighting the need for novel strategies. This study aimed to investigate the efficacy and safety of 5-fluorouracil (5-FU) and vorinostat (SAHA), alone or in combination in preclinical PPGL models.
The growth inhibitory effects of 5-FU and SAHA were investigated in PC-12 cells and human PPGL primary cultures (n = 4) using CCK-8 assays. Drug interactions were evaluated utilizing the Chou-Talalay method. Specific mechanisms were explored via flow cytometry, wound healing, and transwell assays. In vivo efficacy and safety were assessed using mouse subcutaneous xenograft models.
Both monotherapies inhibited PC-12 growth in a dose- and time-dependent manner (5-FU: 0-160 μM and SAHA: 0-80 μM). The combination therapy (20 μM 5-FU + 10 μM SAHA) exhibited a robust synergistic effect with the combination index < 1, achieving 43% growth inhibition in PC-12 cells and nearly 70% in primary cultures, significantly outperforming monotherapies. This combination significantly exacerbated G0/G1 cell cycle arrest and suppressed PC-12 cell migration and invasion. In vivo, the combined treatment reduced final tumor volumes by approximately 50% and significantly decreased the Ki-67 index. Despite mild body weight loss on days 15 and 21, no evident histopathological organ damage was observed.
This study provides the first preclinical evidence that combining SAHA with 5-FU exerts a robust synergistic antitumor effect in PPGLs with no evident histopathological organ damage, laying a strong foundation for developing novel combination therapy for metastatic PPGLs.

PMID:
42859296
Bibliographic data and abstract were imported from PubMed on 11 Oct 2026.

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