Abstract
Androgen deprivation therapy has become the fist-line treatment of metastatic prostate cancer; however, progression to castrate resistance disease occurs in the majority of patients. Thus, there is an urgent need for improvements in therapy for castration-resistant prostate cancer. The aims of the present study were to determine the efficacy somatostatin analogue octreotide (OCT) combined with a low dose of docetaxel (DTX) using castration resistant prostate cancer cells and to investigate the involved molecular mechanisms in vitro. The anti-proliferative and synergism potential effects were determined by MTT assay. Induction of apoptosis was analyzed employing annexing V and propidium iodide staining and flow cytometry. VEGFA, CASP9, CASP3 and ABCB1 gene expression was evaluated by RT-PCR and Q-RT-PCR analysis. OCT in combination with DTX treatments on DU145 cell migration was also evaluated. Investigation revealed that combined administration of DTX and OCT had significant, synergistically greater cytotoxicity than DTX or OCT treatment alone. The combination of the two drugs caused a more marked increase in apoptosis and resulted in greater suppression of invasive potential than either individual agent. There was obvious increase in caspase 3 expression in the OCT alone and two-drug combined treatment groups, however, VEGFA expression was markedly suppressed in them. These results support the conclusion that somatostatin analogues combined with docetaxel may enhance the chemotherapy efficacies through multiple mechanisms in castration-resistant PCa cell line. This work provides a preclinical rationale for the therapeutic strategies to improve the treatment in castrate resistance disease.
Highlights
Prostate cancer (PCa) is the most common cancer which represents a great threat to men’s health
We evaluated the combined effect of DTX and OCT against prostate cancer DU145 and PC3 cells (Fig. S1)
We found that PC3 cells showed more sensitive to DTX than DU145 cells which consistent with the study in vivo (Fig. S5)
Summary
Prostate cancer (PCa) is the most common cancer which represents a great threat to men’s health. Androgen deprivation therapy (ADT) involving surgical or chemical castration is the standard treatment for patients with advanced PCa [1]. Most patients will become refractory to androgen deprivation and progress with castration-resistant diseases [2], usually within 12–24 months from initiation of hormonal therapy [3]. The emergence of aggressive castration-resistant clones during ADT is rationale for taxane-based therapy, which is the only chemotherapy class to show a survival benefit in metastatic castration resistant prostate cancer (CRPC) [4,5]. DTX was reported to exert antiangiogenic effects [10] It reminds us of the early evidence that taxotere could inhibit the proliferation of human umbilical vein endothelial cell proliferation through inhibition of VEGF secretion [11]. It often fails to cure patients, it is important to identify better or alternative therapeutic strategies that reverse chemotherapy resistance and enhance sensitivity to docetaxelbased chemotherapy drugs
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