Page 263 - 2025中醫藥與天然藥物聯合學術研討會-中醫藥與天然藥物的挑戰Ｘ機遇與未來大會手冊

PP-80

Rhapontigenin attenuates renal cancer progression via EREG regulation and

suppression of M2 macrophage polarization

,2
#,1
Hsin-Yu Liu, Chia-Liang Lin*

1 School of Medicine, Chung Shan Medical University
2 Department of Biochemistry, School of Medicine, Chung Shan Medical University
* E-mail: t03742@csmu.edu.tw

Abstract
Stilbenoids are a group of plant-derived polyphenolic compounds with diverse biological
activities, including antioxidant, anti-inflammatory, and anticancer properties. Among them,
rhapontigenin (RHA), a methoxylated stilbenoid, has attracted attention due to its unique
pharmacological profile. Compared with resveratrol, RHA exhibits superior bioavailability and
metabolic stability, underscoring its therapeutic potential. Renal cell carcinoma (RCC), which
accounts for approximately 85–90% of adult kidney cancers, remains associated with poor
clinical outcomes due to its propensity for metastasis and resistance to current therapies.
Therefore, the identification of novel therapeutic agents and predictive biomarkers is urgently
needed. This study comprehensively evaluates the anticancer potential of RHA in RCC, with a
focus on its molecular mechanisms in suppressing tumor progression and remodeling the tumor
immune microenvironment. Our findings demonstrate that RHA significantly inhibits RCC cell
migration and invasion, particularly in 786-O and ACHN cells, by downregulating epiregulin
(EREG) and matrix metalloproteinase-1 (MMP-1), key drivers of extracellular matrix
remodeling and metastasis. Concurrent reductions in pAKT and pERK further indicate that
RHA disrupts oncogenic signaling pathways. Importantly, RHA also impedes the M2
polarization of tumor-associated macrophages (TAMs), thereby attenuating pro-metastatic
immune crosstalk and further restricting RCC invasion. Collectively, these results identify RHA
as a multi-target inhibitor of RCC metastasis through the novel EREG–TAM regulatory axis,
highlighting its dual capacity to modulate tumor-intrinsic pathways and the immune
microenvironment. This study not only provides mechanistic insights into the anti-metastatic
effects of RHA but also positions EREG as a potential biomarker for therapeutic responsiveness,
suggesting a promising role for RHA as a candidate agent in precision therapy for renal cell
carcinoma.

Keywords: Rhapontigenin (RHA); Renal Cell Carcinoma (RCC); Anti-metastatic Mechanisms;
Epiregulin (EREG); Tumor-Associated Macrophages (TAMs)