Transforming Growth Factors-β in Malignant Glioma: Preliminary Studies on Inhibition by Antisense Oligodeoxynucleotides
Type β-transforming growth factors (TGF-β) are multifunctional polypeptides that regulate cell growth and differentiation. TGF-ß1 and TGF-β2 are closely related and resemble the immunosuppressive effects of malignant gliomas. As TGF-ß2 is produced by gliomas, it may contribute to glioma-mediated immunosuppression. To inhibit TGF-β production, a set of 16mer antisense oligodeoxynucleotides (ODNs) was constructed. The glioma cell line U-251 was incubated with 10 μM antisense oligodeoxynucleotides for 24 h. A specific antiproliferative effect was observed for an oligodeoxynucleotide complementary to a region of complete mRNA homology between TGF-ß1 and TGF-ß2. Inhibition of TGF-ß expression could not be verified in a standard Mv-1-Lu bioassay. In this assay TGF-ß inhibits proliferation of Mv-1-Lu cells. Direct treatment of Mv-1-Lu with TGF-ß1 and TGF-ß2 specific antisense as well as unspecific oligodeoxynucleotides resulted in a dose-dependent inhibition of proliferation, indicating direct and unspecific effects of these oligodeoxynucleotides on Mv-1-Lu.
KeywordsMalignant Glioma Glioma Cell Line Lymphokine Activate Killer Antisense Oligodeoxynucleotides Antisense ODNs
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