[Enhanced anti-prostate cancer effect of Sparganii Rhizoma-Curcumae Rhizoma herb pair via synergistic regulation of AR/FOXA1 signaling axis and M2 polarization of tumor-associated macrophages].

This study analyzed the effect of serum containing Sparganii Rhizoma(SR) and Curcumae Rhizoma(CR) herb pair on prostate cancer(PCa) cell proliferation, migration, apoptosis, and immune micro-environment based on the androgen receptor(AR)/forkhead box protein A1(FOXA1) signaling axis and tumor-associated macrophages(TAMs) polarization. SD rats were gavaged with SR, CR to obtain SR-CR-containing serum. Cell counting kit-8(CCK-8), colony formation, wound-healing, and 3D tumor sphere assays were conducted to detect the synergistic inhibitory effect of SR-CR-containing serum on the proliferation and migration of 22RV1 and C4-2B cells. Western blot was employed to examine AR and FOXA1 protein levels. A RAW264.7-C4-2B co-culture model combined with flow cytometry was used to evaluate the effect of SR-CR on macrophage M2 polarization(CD206) and cancer cell apoptosis(Annexin V-FITC/PI). Further, the RM-1 subcutaneous transplanted tumor model was established in C57BL/6J mice to observe the regulation of SR-CR combined medication on tumor volume, spleen index, and intratumoral M2-TAMs ratio. Compared with the single medication group, the results indicated the following changes after 10% SR + 10% CR containing serum intervention for 48 hours. Proliferation, colony formation, and migration ability were significantly lower in two PCa cells(P<0.01)(CI<1), exhibiting a strong synergistic effect. AR and FOXA1 expression was significantly down-regulated(P<0.05), and 3D tumor sphere volume was decreased(P<0.05). In the co-culture system, the M2-TAMs ratio was significantly reduced while cancer cell apoptosis was significantly increased(P<0.01). In vivo experiment demonstrated that, compared with the control group, the SR-CR synergy group displayed lower tumor weight and tumor volume, elevated spleen index, and fewer M2-TAMs within tumors(all P<0.05). In summary, the SR-CR herbal pair, through mutual reinforcement(Xiang-Xu), concurrently inhibits the AR/FOXA1 signaling axis and arrests M2-TAMs polarization, thereby enhancing anti-PCa efficacy.