BERKELEY, CA (UroToday.com) - Docetaxel plays a unique role in the management of advanced, hormone-refractory prostate cancer (HRPC), so that when the tumour acquires resistance to docetaxel, an active second-line chemotherapy is lacking. Thus, enhancing docetaxel activity in HRPC is of major clinical interest.

In addition to the successful application of somatostatin (SST) analogues in relieving symptoms produced by endocrine tumours, antiproliferative action of SST analogues was reported in various tumours.

We investigate at an experimental level the combination between docetaxel and the analogue of SST, lanreotide, as they can interact at the level of the MAPK pathway. We used as model the androgen-independent PC3 cell line, either sensitive or made resistant to docetaxel.

SST receptors (SSTR) type 2 and 5 were expressed in the PC3 cell line, confirming its suitability to be used as a model in the study . There was no effect on cellular proliferation when lanreotide was applied alone, both in PC3wt and PC3R cells.

Similarly, non additional effect on the inhibition of cell proliferation was observed when lanreotide was combined with docetaxel, in PC3 wt, but the same combination was able to inhibit cell growth in PC3R cells. In details, our study showed that lanreotide has enhancing effects on docetaxel-induces toxicity on PC3R cells and this effect depended on the level of resistance of the cells, so that the presence of lanreotide was able to partly restore the sensitivity to docetaxel.

The growth inhibition induced by the combined treatment docetaxel plus lanreotide was not mediated by a modulation of MAPK activation, but possibly by cyclin/CDK complexes, as shown by the enhanced expression of p27 after exposure to each drug individually, and in the combined treatment.

Our data suggest that lanreotide could act as a blocker in ‘high-resistance’ PC3R cells. Inhibition of the ABC transporter family gene Multi Drug Resistance MDR1 (Pgp) could partially reverse pharmaco-resistance and might thus enhance the cellular retention of Pgp substrate drugs, such as docetaxel.

Taken together, the present results suggest a new and different approach in using SST analogues in prostate cancer, in which lanreotide could interact with docetaxel in PC3R cells, with possible explanatory mechanisms involving the regulation of the interaction of Pgp-mediated docetaxel resistance through lanreotide. Thus, if our data will be confirmed, the therapeutic use of lanreotide, could be extended, in combination with docetaxel, to non-neuroendocrine prostate cancer. These data introduce a promising, unexplored therapeutic approach in treating hormone-refractory prostate cancer.

Written by
Cristiana Lo Nigro, MD, as part of Beyond the Abstract on UroToday.com. This initiative offers a method of publishing for the professional urology community. Authors are given an opportunity to expand on the circumstances, limitations etc... of their research by referencing the published abstract.

The Combination of Docetaxel and the Somatostatin Analogue Lanreotide on Androgen-Independent Docetaxel-Resistant Prostate Cancer: Experimental Data - Abstract

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