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Updated: Aug 25, 2025
An Orthotopic Murine Model of Human Prostate Cancer Metastasis
Published on: September 18, 2013
Resveratrol inhibits TRAF6/PTCH/SMO signal and regulates prostate cancer progression
Jianping Li1, Ziming Wang1, Hecheng Li1
1Department of Urology, The Second Affiliated Hospital of Xi'an Jiaotong University, No. 157, Xiwu Road, Xincheng Road, Xi'an, 710004 Shanxi People's Republic of China.
Abstract:
Prostate cancer (PC) is one of the most common types of cancers among men, referring to the uncontrolled growth of the prostate gland. It is increasingly recognized that the interaction of the glioma-associated oncogene (GLI) pathway and androgen receptor affects PC progression. Nevertheless, the effects of resveratrol on PC progression via Hedgehog (HH) signaling remain unexplored. In this study, the castration-sensitive and castration-resistant xenograft models in mice are systematically established using two different PC cell lines (LNCaP and PC-3). Further, the Western blotting, immunohistochemistry, MTT, Transwell, and RT-qPCR analyses are performed to verify the mechanistic views of resveratrol on PC and HH signals in vitro and in vivo. Resveratrol showed epithelial-mesenchymal transition (EMT) progression, inhibiting the tumor size and expression levels of vimentin, vascular endothelial growth factor (VEGF), and matrix metalloproteinases (MMP) 7, as well as upregulating the expression profiles the E-cadherin and Annexin 2. Moreover, resveratrol inhibited the hedgehog (HH) signals and tumor necrosis factor receptor (TNFR)-associated factor 6 (TRAF6) levels exhibiting the therapeutic action on castration-sensitive and castration-resistant PC cell lines. In summary, the overexpression of TRAF6 enhanced the viability and EMT progression of cancer cells. The resveratrol could alleviate the TRAF6 effect and regulate the HH signal to affect PC progression.
Supplementary Information:
The online version contains supplementary material available at 10.1007/s10616-022-00544-0.
Insights
Resveratrol effectively inhibits prostate cancer (PC) progression by regulating Hedgehog (HH) signaling and reducing tumor necrosis factor receptor-associated factor 6 (TRAF6) levels. This natural compound demonstrates therapeutic potential against both castration-sensitive and castration-resistant PC.
Area of Science:
- Oncology
- Molecular Biology
- Pharmacology
Background:
- Prostate cancer (PC) is a prevalent malignancy in men.
- The interplay between the glioma-associated oncogene (GLI) pathway and androgen receptor influences PC progression.
- The impact of resveratrol on PC via Hedgehog (HH) signaling is not well understood.
Purpose of the Study:
- To investigate the effects of resveratrol on prostate cancer progression, focusing on Hedgehog (HH) signaling.
- To elucidate the mechanisms by which resveratrol influences cancer cell behavior and signaling pathways in vitro and in vivo.
Main Methods:
- Establishment of castration-sensitive and castration-resistant xenograft mouse models using LNCaP and PC-3 cell lines.
- In vitro and in vivo analyses including Western blotting, immunohistochemistry, MTT assays, Transwell migration assays, and RT-qPCR.
- Evaluation of epithelial-mesenchymal transition (EMT) markers, HH signaling components, and TRAF6 expression.
Main Results:
- Resveratrol inhibited tumor growth and suppressed EMT progression, decreasing levels of vimentin, VEGF, and MMP7 while increasing E-cadherin and Annexin 2.
- Resveratrol effectively inhibited Hedgehog (HH) signaling and reduced tumor necrosis factor receptor-associated factor 6 (TRAF6) levels.
- Overexpression of TRAF6 was found to enhance cancer cell viability and EMT progression, effects which were alleviated by resveratrol.
Conclusions:
- Resveratrol exhibits therapeutic effects against both castration-sensitive and castration-resistant prostate cancer.
- Resveratrol modulates the HH signaling pathway and alleviates the pro-cancer effects of TRAF6.
- These findings suggest resveratrol as a potential therapeutic agent for prostate cancer management.
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