Ginsenoside Rg3 synergizes with near-infrared photothermal therapy to suppress prostate cancer progression by
Haiping Zhang1, Ying Chang2, Qiang Fu3
1Department of Central Laboratory, Yanbian University Hospital, Yanji, China; Department of Oncology, Yanbian University Hospital, Yanji, China; Department of Pathology and Cancer Research Center, Yanbian University, Yanji, China.
Abstract:
Prostate cancer (PCa) progression and therapeutic resistance are largely driven by aberrant oncogenic signaling and an immunosuppressive microenvironment. Ginsenoside Rg3, a natural saponin from Panax ginseng, exhibits antitumor and immunomodulatory activity, but its therapeutic efficacy is limited when used as a monotherapy. Here, we investigated the synergistic potential of combining Rg3 with near-infrared (NIR) exposure in PCa. In PC-3 and DU145 cells, co-treatment with Rg3 and NIR synergistically inhibited proliferation, migration, and angiogenesis, while promoting apoptosis and reversal of epithelial-mesenchymal transition. Bioinformatic and molecular analyses identified the RAS/RAF/ERK pathway as a key target, with Rg3 showing a strong potential to interact with RAS and suppressing downstream phosphorylation of RAF and ERK; pharmacologic RAS activation partially reversed these effects. Beyond direct tumor inhibition, the combination also enhanced macrophage ARL11 expression and reprogrammed tumor-associated macrophages from an M2 to M1 phenotype through suppression of tumor RAS signaling. In xenograft models, Rg3 and NIR co-treatment markedly reduced tumor growth without systemic toxicity and increased M1 infiltration within tumor tissues. Collectively, these findings demonstrate that Rg3 combined with NIR exerts potent and safe antitumor activity by concurrently targeting tumor-intrinsic RAS/RAF/ERK signaling and ARL11-mediated immune reprogramming, offering a promising multimodal strategy for PCa therapy.
Insights
Ginsenoside Rg3 combined with near-infrared (NIR) therapy shows synergistic effects against prostate cancer (PCa). This multimodal strategy targets tumor signaling and reprograms the immune microenvironment for potent and safe antitumor activity.
Area of Science:
- Oncology
- Immunology
- Pharmacology
Background:
- Prostate cancer (PCa) progression is driven by oncogenic signaling and an immunosuppressive tumor microenvironment.
- Ginsenoside Rg3 (Rg3) has antitumor properties but limited efficacy as a monotherapy.
- Therapeutic resistance in PCa necessitates novel combination strategies.
Purpose of the Study:
- To investigate the synergistic potential of combining Rg3 with near-infrared (NIR) exposure for PCa treatment.
- To elucidate the underlying molecular mechanisms of the combined therapy.
- To evaluate the efficacy and safety of the Rg3-NIR combination in preclinical models.
Main Methods:
- In vitro studies using PC-3 and DU145 PCa cell lines.
- Bioinformatic and molecular analyses to identify signaling pathways.
- In vivo xenograft studies in mouse models.
- Assessment of proliferation, migration, apoptosis, angiogenesis, epithelial-mesenchymal transition (EMT), macrophage polarization, and tumor growth.
Main Results:
- Rg3 and NIR synergistically inhibited PCa cell proliferation, migration, and angiogenesis, while promoting apoptosis and reversing EMT.
- The combination targeted the RAS/RAF/ERK pathway, with Rg3 interacting with RAS and suppressing RAF/ERK phosphorylation.
- Rg3-NIR enhanced macrophage ARL11 expression, reprogramming M2 tumor-associated macrophages (TAMs) to M1 phenotype via RAS signaling suppression.
- In vivo, Rg3-NIR significantly reduced tumor growth without systemic toxicity and increased M1 macrophage infiltration.
Conclusions:
- The combination of Rg3 and NIR demonstrates potent and safe antitumor activity in PCa.
- This multimodal strategy concurrently targets tumor-intrinsic RAS/RAF/ERK signaling and ARL11-mediated immune reprogramming.
- Rg3-NIR represents a promising therapeutic approach for PCa, addressing both tumor growth and the immune microenvironment.
