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


METHODS
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.


RESULTS
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.


CONCLUSIONS
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.
Lo Nigro
Cristiana
C
Laboratorio di Oncologia Translazionale, ASO S. Croce e Carle, Cuneo, Italy. lonigro.c@ospedale.cuneo.it
Maffi
Monica
M
Fischel
Jean Louis
JL
Formento
Patricia
P
Milano
Gerard
G
Merlano
Marco
M
D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D000077143:Docetaxel; D004341:Drug Evaluation; D019008:Drug Resistance, Neoplasm; D006801:Humans; D008297:Male; D020929:Mitogen-Activated Protein Kinase Kinases / Q000187:drug effects; D009376:Neoplasms, Hormone-Dependent / Q000188:drug therapy*; D010456:Peptides, Cyclic / Q000008:administration & dosage; D011471:Prostatic Neoplasms / Q000188:drug therapy*; D015398:Signal Transduction / Q000187:drug effects; D013004:Somatostatin / Q000008:administration & dosage / Q000031:analogs & derivatives; D043823:Taxoids / Q000008:administration & dosage
D010456:Peptides, Cyclic; D043823:Taxoids; C060347:lanreotide; D000077143:Docetaxel; D013004:Somatostatin; D020929:Mitogen-Activated Protein Kinase Kinases