Paradoxical and Contradictory Effects of Imatinib in Two Cell Line Models of Hormone-Refractory Prostate Cancer

摘要: BACKGROUND Imatinib mesylate is a chemotherapeutic drug that inhibits the tyrosine kinase activity of c-KIT and has been successfully used to treat leukemias some solid tumors. However, its application for treatment hormone-refractory prostate cancer (HRPC) shown modest effectiveness did not follow outcomes in cultured cells or animal models. Moreover, molecular pathways by which imatinib induces cytotoxicity are poorly characterized. METHODS Two cell line models HRPC (DU145 PC3) were exposed 20 μM 6–72 hr. MTS assay was assess viability during course experiment. Gene expression analysis c-KIT, cell-cycle apoptosis regulators, angiogenic factors determined means real-time PCR, western blot, and/or immunocytochemistry. The enzymatic effector, caspase-3, colorimetric assay. RESULTS Imatinib significantly decreased DU145 but paradoxically augmented PC3 cells. displayed diminished anti-apoptotic Bcl-2 protein levels caspase-8 -9, as well as, increased caspase-3 response imatinib. No differences existed on apoptosis-related proteins treated with imatinib, though decreased. mRNA factor VEGF DU145-treated cells, whereas an opposite effect seen PC3. In addition, it present differential variants. CONCLUSION DU145 contradictory behavior underpinned distinct pattern (or activity) target regulators cell-cycle, apoptosis, angiogenesis. paradoxical may be related variants. findings helped understand discrepancies efficacy therapeutic option HRPC. Prostate 75:923–935, 2015. © 2015 Wiley Periodicals, Inc.