CORRELATION OF GLIOMA CELL REGRESSION WITH INHIBITION OF INSULIN-LIKE-GROWTH-FACTOR-1 AND INSULIN-LIKE GROWTH FACTOR-BINDING PROTEIN-2 EXPRESSION

To explore the antitumor effect of insulin-like growth factor 1 (IGF-I ) antisense RNA and the interaction of IGF-I with insulin-like growth factor-binding proteins (IGFBPs) in glioma cells, a recombinant retrov irus expressing IGF-I antisense RNA was constructed and introduced int o C6 glioma cells. IGF-I antisense RNA reverses the transformed phenot ype in glioma cells and inhibits glioma cell growth by blocking overex pression of endogenous IGF-I. Expression of IGFBP-2 is increased in gl ioma cells as compared with normal adult glial cells. IGF-I antisense RNA also inhibits expression of IGFBP-2 in glioma cells, but does not influence expression of the other IGFBPs. Although IGFBP-2 in conditio ned medium from wild-type C6 cell cultures itself does not directly in fluence glioma cell growth, it synergistically enhances exogenous IGF- I-mediated DNA synthesis in IGF-I-negative C6 cells. These findings in dicate the inhibitory effect of IGF-I antisense RNA on growth and deve lopment of glioma cells. IGF-I-dependent glioma cell growth may, in so me circumstances, require IGFBP-2 as a cofactor. The antitumor effect of IGF-I antisense RNA is also associated with inhibition of IGFBP-2 e xpression.