The combination of docetaxel and the somatostatin analogue lanreotide on androgen-independent docetaxel-resistant prostate cancer: experimental data.

Abstract

To evaluate the effects of the association between docetaxel and the somatostatin analogue lanreotide on the androgen-independent prostate cancer cell line PC3, either sensitive or made resistant to docetaxel (PC3R), as new drugs and new combinations have promising clinical activity in hormone-refractory prostate cancer. We examined the effect of docetaxel and lanreotide on cell proliferation, with analysis of the mitogen-activated protein kinase pathway and expression of cell-cycle regulatory proteins. Combined treatment with docetaxel and lanreotide inhibited PC3 cell growth in vitro through an enhanced induction of cell death, compared with treatment with either agent alone; this result was particularly evident on PC3R cells. The results suggested that lanreotide could act as a P glycoprotein inhibitor in PC3R cells. The present results provide a promising therapeutic approach for using somatostatin analogues in hormone-refractory prostate cancer, in which lanreotide could interact with docetaxel in PC3R cells, with possible explanatory mechanisms which involve P glycoprotein-mediated docetaxel resistance.