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In vitro cytotoxic effects of imatinib in combination with anticancer drugs in human prostate cancer cell lines
Author(s) -
Kübler Hubert R.,
Randenborgh Heiner van,
Treiber Uwe,
Wutzler Sebastian,
Battistel Carolus,
Lehmer Antonie,
Wagenpfeil Stefan,
Hartung Rudolf,
Paul Roger
Publication year - 2004
Publication title -
the prostate
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.295
H-Index - 123
eISSN - 1097-0045
pISSN - 0270-4137
DOI - 10.1002/pros.20201
Subject(s) - lncap , imatinib , docetaxel , estramustine , platelet derived growth factor receptor , pharmacology , tyrosine kinase , medicine , prostate cancer , cancer research , etoposide , cytotoxic t cell , tyrosine kinase inhibitor , cancer , biology , in vitro , chemotherapy , growth factor , receptor , biochemistry , prostate disease , myeloid leukemia
Abstract BACKGROUND The platelet‐derived growth factor receptor (PDFG‐r), a tyrosine kinase, is expressed in 88% of primary prostate cancer and in 80% of the metastases. The tyrosine kinase inhibitor imatinib blocks the PDGF signaling pathway by inhibiting PDGF‐r autophosphorylation. We examined the cytotoxic effects of imatinib in combination with other anticancer agents in the human prostate cancer cell lines LNCaP, PC‐3, and DU 145. METHODS The cells were exposed to imatinib and to the other drugs simultaneously for 5 days. Cell growth inhibition was determined by XTT assay. The cytotoxic effects in combinations were evaluated at the inhibitory concentration of 50% level by the isobologram. RESULTS Imatinib produced additive effects with estramustine phosphate (EMP) and 4‐hydroperoxy‐cyclophosphamide in all three cell lines. In combination with etoposide imatinib produced additive effects in two of three cell lines. Imatinib with docetaxel produced antagonistic effects in PC‐3 and additive to antagonistic effects in LNCaP and DU 145 cells. CONCLUSIONS The simultaneous exposure of imatinib and EMP would be effective against hormone sensitive and hormone insensitive cell lines and this combination should be evaluated in clinical trials. In contrast, the simultaneous exposure of imatinib and docetaxel would have little therapeutic efficacy. Although there are gaps between in vitro studies and clinical trials, the present findings provide useful information for the establishment of clinical protocols involving imatinib in hormone‐refractory prostate cancer. © 2004 Wiley‐Liss, Inc.