2. Academic Validation
  3. Ginsenoside Rg3 synergizes with near-infrared photothermal therapy to suppress prostate cancer progression by inhibiting RAS signaling and enhancing ARL11-mediated macrophage reprogramming

Ginsenoside Rg3 synergizes with near-infrared photothermal therapy to suppress prostate cancer progression by inhibiting RAS signaling and enhancing ARL11-mediated macrophage reprogramming

  • Int Immunopharmacol. 2026 Apr 15:175:116417. doi: 10.1016/j.intimp.2026.116417.
Haiping Zhang 1,  Ying Chang 2,  Qiang Fu 3,  Tiefeng Jin 4,  Songnan Zhang 5,  Meihua Zhang 6
Affiliations

Affiliations

  • 1 Department 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.
  • 2 Department of Central Laboratory, Yanbian University Hospital, Yanji, China; Department of Pathology and Cancer Research Center, Yanbian University, Yanji, China.
  • 3 Department of Central Laboratory, Yanbian University Hospital, Yanji, China; Department of Pathology and Cancer Research Center, Yanbian University, Yanji, China; Department of Ultrasound Medical Center, Honghui Hospital, Xi'an Jiaotong University, Xi' an, Shaanxi, China.
  • 4 Department of Central Laboratory, Yanbian University Hospital, Yanji, China; Department of Pathology and Cancer Research Center, Yanbian University, Yanji, China; Key Laboratory of Natural Medicines of the Changbai Mountain, Ministry of Education, Yanji, China. Electronic address: [email protected].
  • 5 Department of Central Laboratory, Yanbian University Hospital, Yanji, China; Department of Oncology, Yanbian University Hospital, Yanji, China. Electronic address: [email protected].
  • 6 Department of Central Laboratory, Yanbian University Hospital, Yanji, China. Electronic address: [email protected].
PMID: 41734586 DOI: 10.1016/j.intimp.2026.116417
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.

Keywords

ARL11; Ginsenoside Rg3; Near-infrared photothermal therapy; Prostate cancer; RAS/RAF/ERK signaling pathway; Tumor-associated macrophages.

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