Interleukin-6 induces VEGF secretion from prostate cancer cells in a manner independent of androgen receptor activation.

摘要: Background The reduced androgen-sensitivity of prostate cancer (PCa) cells is an important clinical development because its association with the cells' progression to castration-resistant (CRPC). During androgen deprivation therapy (ADT), stroma-derived growth factors and cytokines can activate receptor (AR). For example, IL-6 a multifunctional cytokine that involved in malignancy PCa through AR activation. In present study, we used androgen-sensitive human cell line (LNCaP) sublines investigate relationship between responsiveness treatment cellular signaling pathway. Methods androgen-low-sensitive F10 E9 were obtained from LNCaP by limiting dilution method regular culture condition. contrast, androgen-insensitive AIDL established continuous passaging hormone-depleted Original carcinoma-associated fibroblasts (CAFs) PCaSC-8 PCaSC-9 isolated needle biopsy samples patients. Results derived patients, secretion was generally higher than observed normal fibroblasts. not detected sublines. soluble but suppressed LNCaP, F10, it accompanied neuroendocrine-like differentiation. Induction PSA IL-6-treated cells. VEGF strongly induced IL-6-induced significantly PI3K inhibitor (LY294002) inhibited phosphorylation Akt. Conclusions Our results suggest might induce manner independent To prevent secretion, inhibition PI3K/AKT pathway could be pharmacological goal regardless ADT.