The effect of tyrosine kinase inhibitors, tyrphostins: AG1024 and SU1498, on autocrine growth of prostate cancer cells (DU145).
It is well established that autocrine growth of human prostate cancer cell line DU145 is dependent on TGF (EGF)/EGFR loop. However, the participation of several other growth factors in proliferation of DU145 cells has been also proposed. We employed two selective tyrosine kinase inhibitors (tyrphostins): AG1024 (an IGFIR inhibitor) and SU1498 (a VEGFR2 inhibitor) for growth regulation of DU145 cells, cultured in chemically defined DMEM/F12 medium. Both the tested compounds inhibited autocrine growth of DU145 cells at similar concentration values (IC50 approximately 2.5 microM). The tyrphostins arrested cell growth of DU145 in G1 phase, similarly as inhibitors of EGFR. However, in contrast to selective inhibitors of EGFR, neither AG1024, nor SU1498 (at concentration < or =10 microM) decreased the viability of the investigated cells. These results strongly suggest that autocrine growth of DU145 cells is stimulated by, at least, three autocrine loops: TGFalpha(EGF)/EGFR, IGFII/IGFIr and VEGF/VEGFR2(VEGFR1). These data support the hypothesis of multi-loops growth regulation of metastatic prostate cancer cell lines.
Department of General Biochemistry, Faculty of Biochemistry, Biophysics and Biotechnology, Jagiellonian University, Cracow, Poland.
Joanna
J
Kisielewska
Janusz
J
Ligeza
Andrzej
A
Klein
D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D019898:Autocrine Communication / Q000187:drug effects*; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D002934:Cinnamates / Q000494:pharmacology*; D017077:Culture Media, Conditioned; D004305:Dose-Response Relationship, Drug; D006801:Humans; D008297:Male; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology*; D047428:Protein Kinase Inhibitors / Q000494:pharmacology*; D020032:Tyrphostins / Q000494:pharmacology*
D000970:Antineoplastic Agents; D002934:Cinnamates; D017077:Culture Media, Conditioned; D047428:Protein Kinase Inhibitors; C483044:SU 1498; D020032:Tyrphostins; C447031:tyrphostin AG 1024; D017239:Paclitaxel