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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. MATERIALS AND 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. CONCLUSION 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.

We concluded that the expression of the EPOR in Cal-166 cells does not seem essential for their growth and that administration of EPO does not affect RT efficacy.

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6058 Background: Anemia frequently occurs in Head and Neck Squamous Cell Carcinoma (HNSCC) and has been associated with decreased quality of life, impaired treatment outcomes and shortened survival. Furthermore, anemia is a causative factor of tumor hypoxia, which compromises the efficacy of radiotherapy (RT). In order to circumvent the negative effects of anemia, several attempts have been made including the use of EPO, particularly in HNSCC. However, recent clinical data suggest a detrimental effect of EPO on survival for HNSCC patients treated with RT plus EPO. Methods: The HNSCC CAL-166 cell line, which is wild type p53 and expresses the EPO receptor (EPOR), was investigated in the present study; a MTT test was used to examine the effects of EPO on the cellular response to RT. Extended preliminary experiments were performed to standardize the conditions (time of exposure to hypoxia and time to return of normal culture conditions) and the administration of radiation (fractionated or in single dose) to optimize the effects of hypoxia on radiation response. Cells were exposed to a X-rays source at escalating doses from 2–20 Gy and showed classical dose- response curves. Hypoxia was mimed using a ‘Bug-Box‘ anaerobic workstation for 24–48 hours. Results: After a single RT dose of 10 Gy, the data confirmed the negative effect of hypoxia, directly related to the duration of hypoxia (% surviving cells when irradiated in normoxia: 43.95 ± 4.24; when irradiated after 24 hours of hypoxia, 62.4 ± 8.3 or after 48 hours, % surviving cells 70.8 ± 7.4; p = 0.001 versus RT in normoxia). The addition of EPO, from 24 hours before RT to 72 hours after, until MTT test, did not modify the cytotoxic effect of RT in hypoxic, but also in oxic conditions. Conclusions: These preliminary data do not support a direct negative effect of EPO when treating EPOR positive tumor cells with irradiation. Additional data concern the molecular impact of EPO on tumor cell lines with examination of EPOR, HIF-1 alpha and EGFR. No significant financial relationships to disclose.