Synergism and Mechanism of Octreotide on Docetaxel-resistant Cancer Cell DU145

Objective To investigate the effects and possible mechanisms of Octreotide on the drug sensitivity of Docetaxel resistant DU145 cells in vitro. Methods The inhibitory effects of Docetaxel, Octreotide and Octreotide (100nM) combined with Docetaxel at different concentrations on DU145 cell were tested by MTT assay. The following-up experiments were divided into four groups, control group, OCT(100nM) group, DTX(10nM)/OCT(100nM) group and DTX(10nM) group. The mRNA levels of Homo sapiens vascular endothelial growth factor A (VEGFA)﹑apoptosis-related cysteine peptidase (Caspase9)﹑caspase 3, apoptosisrelated cysteine peptidase (Caspase3) and ATP-binding cassette, sub-family B (MDR/TAP), member 1 (ABCB1) in human prostate cancer cell line DU145 were detected by RT-PCR; The migration ability of cells in each group was detected by scratch test. Results The proliferation inhibitory rate of DU145 cell in DTX(10nM)/OCT(100nM) group (55.70±0.08)％was higher than that in Docetaxel (26.23±0.03)％or Octreotide group(24.77±0.04)％,(P﹤0.01). Octreotide increased the drug sensitivity of DU145 cells against Docetaxel, with IC50 value decreasing significantly(24.55±0.36) vs. (11.85±0.25）nM, P﹤0.01. The gene expression of Caspase3 and Caspase9 in the drug combination group were higher than those in other groups, while the expression of VEGFA decreased in the drug combination group(P﹤0.01). In addition, there was no difference of ABCB1 mRNA level in all groups. The cell ability of migration in the combination group was lower than those in other groups. Conclusion The increased drug sensitivity and reduced migration ability of DU145 cell lines affected by Octreotide may be related to the increased expression of Caspase3 and Caspase9 and reduced expression of VEGFA.