Taxotere and vincristine inhibit the secretion of the angiogenesis inducing vascular endothelial growth factor (VEGF) by wild-type and drug-resistant human leukemia T-cell lines.

摘要: Recent studies have shown that angiogenesis, which is induced by VEGF, may be involved in the pathogenesis of hematopoietic malignancies. A human leukemia model consisting T-lymphoblastic CEM/0, 7 monoclonal refractory clones resistant to both cytosine arabinoside (ara-C) and L-asparaginase (ASNase), Jurkat/E6-1 U937, representing leukemic blasts from relapsed patients with leukemias was investigated for secretion VEGF before after treatment various agents. The cell line, Jurkat/E6-1, used as negative control, has been characterized not expressing mRNA nor protein, did secrete VEGF. With no treatment, positive secreted highest concentration 1612.7 pg/ml. CEM/O wild type line 5 other drug-resistant at levels ranging 180.9 414.2 Two CEM clones, CEM/ara-C/G/ASNase-0.5-1 CEM/ara-C/G/ASNase-1-1, lacked production. Docetaxel (Taxotere, TXR), Vincristine (VCR), ASNase, Fit-1/Fc chimera, a specific inhibitor VEGF-dependent umbilical vein endothelial (HUVEC) proliferation, were tested inhibition secretion. Treatment lines 2 microg/ml Flt-1/Fc chimera 24 hours completely inhibited detection limit assay (<10pg/ml). After incubation cells appeared undergoing apoptosis, based on microphotography examination, suggesting could an autocrine loop promote survival cells. 0.5, 1, Flt-1/FC 48 demonstrated 15-25% growth MTT assay. Strong culture media observed 10 microM TXR or 0.1 VCR wild-type except CEM/ara-C/I, comparison controls. In contrast, 1 IU/ml T-cell protein inhibitor, CEM/0 3 myeloid U937 line. We conclude actively vitro. VCR, but strongly inhibit production, this factor mechanism antileukemic activity. Moreover, examined here constitute useful study antiangiogenic drugs, alone combination established drug regimens against leukemias.