Journal of traditional and complementary medicine · 2025
Zhoushi Qiling decoction inhibits neuregulin 1 secreted from cancer-associated fibroblasts to ameliorate enzalutamide resistance in prostate cancer.
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Wang Chunyu, Cao Hongwen, Sun Peng, Chen Lei, Feng Yigeng, Gao Renjie
Аннотация
BACKGROUND AND AIM: Zhoushi Qiling decoction (ZQD) has emerged as a promising therapeutic agent for improving outcomes in prostate cancer treatment. This study aimed to evaluate the efficacy of ZQD on enzalutamide-resistant prostate cancer cells and to elucidates the underlying mechanisms.
EXPERIMENTAL PROCEDURE: A co-culture model consisting of cancer-associated fibroblasts (CAFs) and enzalutamide-resistant prostate cancer cells was established and treated with ZQD-containing serum. Cell proliferation and viability were assessed using colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The anti-tumor effects of ZQD were further evaluated in an in vivo xenograft model using enzalutamide-resistant PC3-EnzR cells treated with ZQD for 28 days. Expression of relevant biomarkers in cell lines and tumor tissues was analyzed by qRT-PCR and Western blotting.
RESULTS: ZQD-containing serum inhibited the expression of neuregulin 1 (NRG1) in CAFs. It also reversed CAF-induced enzalutamide resistance and reduced CAF-stimulated proliferation of enzalutamide-resistant prostate cancer cells. In addition, ZQD suppressed NRG1 secretion and phosphorylation of human epidermal growth factor receptor 3 (HER3) in these cells. The serum also demonstrated inhibitory effects on matrix metalloproteinases (MMP-1 and MMP-9) in enzalutamide-resistant prostate cancer cells. In vivo, ZQD significantly suppressed tumor growth and reduced NRG1 expression.
CONCLUSION: ZQD effectively inhibits NRG1 secretion from CAFs and mitigates enzalutamide resistance in prostate cancer. These findings provide a scientific basis for the potential clinical application of ZQD in overcoming enzalutamide resistance in prostate cancer treatment.
EXPERIMENTAL PROCEDURE: A co-culture model consisting of cancer-associated fibroblasts (CAFs) and enzalutamide-resistant prostate cancer cells was established and treated with ZQD-containing serum. Cell proliferation and viability were assessed using colony formation and 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide assays. The anti-tumor effects of ZQD were further evaluated in an in vivo xenograft model using enzalutamide-resistant PC3-EnzR cells treated with ZQD for 28 days. Expression of relevant biomarkers in cell lines and tumor tissues was analyzed by qRT-PCR and Western blotting.
RESULTS: ZQD-containing serum inhibited the expression of neuregulin 1 (NRG1) in CAFs. It also reversed CAF-induced enzalutamide resistance and reduced CAF-stimulated proliferation of enzalutamide-resistant prostate cancer cells. In addition, ZQD suppressed NRG1 secretion and phosphorylation of human epidermal growth factor receptor 3 (HER3) in these cells. The serum also demonstrated inhibitory effects on matrix metalloproteinases (MMP-1 and MMP-9) in enzalutamide-resistant prostate cancer cells. In vivo, ZQD significantly suppressed tumor growth and reduced NRG1 expression.
CONCLUSION: ZQD effectively inhibits NRG1 secretion from CAFs and mitigates enzalutamide resistance in prostate cancer. These findings provide a scientific basis for the potential clinical application of ZQD in overcoming enzalutamide resistance in prostate cancer treatment.