Growth inhibition of rat osteosarcoma and malignant fibrous histiocytoma cells by tyrosine kinase inhibitor STI571.
STI571 is a 2-phenylaminopyrimide derivative that was designed as an Abl tyrosine kinase inhibitor, but it is also effective against platelet-derived growth factor receptor (PDGFR) and c-Kit tyrosine kinase. Recent studies have demonstrated that STI571 inhibits the growth of several tumors in which PDGF or c-kit play an important role in tumor pathogenesis. We have recently established rat osteosarcoma and malignant fibrous histiocytoma (MFH) cell lines. RT-PCR analysis revealed that MFH and osteosarcoma cell lines expressed high and very low levels of PDGFR alpha respectively, and that all cell lines expressed similar levels of PDGFR beta. The level of c-kit mRNA expression were almost negligible hardly in all cell lines. The effect of STI571 on cellular growth measured by MTS colorimetric dye reduction showed that the growth of each cell line was inhibited in a dose- and time-dependent manner. STI571 (10 microM) inhibited the rates of cell growth of MFH cells by up to 40% and of osteosaroma cells by only to 20% after 72 hours. These data suggested that STI571 tyrosine kinase inhibitor plays a role in blocking or slowing the rate of growth of MFH and osteosarcoma cells expressing tyrosine kinase type receptor.
Yoshitani
Kazuhiro
K
Department of Orthopedic Surgery, Nara Medical University, 840 Shijyo-cho, Kashihara, Nara 634-8522, Japan.
Honoki
Kanya
K
Morishita
Toru
T
Kido
Akira
A
Miyauchi
Yoshizumi
Y
Mii
Yoshio
Y
Takakura
Yoshinori
Y
D000818:Animals; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D001549:Benzamides; D001859:Bone Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D018219:Histiocytoma, Benign Fibrous / Q000188:drug therapy* / Q000473:pathology; D000068877:Imatinib Mesylate; D012516:Osteosarcoma / Q000188:drug therapy* / Q000473:pathology; D010879:Piperazines / Q000627:therapeutic use*; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors*; D019009:Proto-Oncogene Proteins c-kit / Q000235:genetics; D011743:Pyrimidines / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics; D051381:Rats
D000970:Antineoplastic Agents; D001549:Benzamides; D010879:Piperazines; D011743:Pyrimidines; D012333:RNA, Messenger; D000068877:Imatinib Mesylate; D011505:Protein-Tyrosine Kinases; D019009:Proto-Oncogene Proteins c-kit