Objective: To observe the synergistic effects of docetaxol and retinoic acid on prostate cancer cell line PC-3 in vitro and in vivo.
Methods: Cell morphology, MTT, flow cytometry, immunocytochemical method were used to observe the effects of 10(-6) mol/L, 10(-7) mol/L, 10(-8) mol/L docetaxol and 10(-5) mol/L, 10(-6) mol/L, 10(-7) mol/L retinoic acid on prostate cancer cell line PC-3 in single or synergistic administration ways for 24 and 48 hours in vitro. Male BALB/C-nu mice with PC-3 prostate cancer cell lines were treated by docetaxol and retinoic acid singly or synergistically in vivo. Serum PSA of mice, weights of mice and PSA expression in xenograft tumors of mice by immunohistochemical method were measured.
Results: Above 10(-6) mol/L retinoic acid enhanced the growth suppression (suppression ratio > or = 69.2%, P<0.01), apoptosis (Apoptosis ratio > or = 23.8%, P<0.05) and down-regulation of the expression of cyclin D1 (expression ratio < or = 14.2%, P<0.05) induced by above 10(-7) mol/L docetaxol in PC-3 cells. Retinoic acid changed the ratio of G2/M phase induced by docetaxol from 70.3% to 54.6%, and reversed the G2/M arrest partially (P<0.05). Mean serum PSA of mice [(43+/-11) ng/ml], weight of xenograft tumors [(2.8+/-0.4) g] and PSA expression in tumors [(26+/-3.2)%] with PC-3 prostate cancer cell lines of nude mice were decreased significantly in docetaxol combined with retinoic acid group than in control group except weight of mice [(20.3+/-1.1) g].
Conclusion: Retinoic acid can enhance the growth suppression and apoptosis induced by docetaxol in synergistic way in vitro and in vivo, thus showing their great potential in the treatment of androgen-independent carcinoma of prostate.