TMET-18. TARGETING AMINO ACID METABOLIC VULNERABILITIES IN GLIOBLASTOMA

Abstract Tumor cells have different metabolism from normal cell, which is called as cancer metabolism. In cells, asparagine provided by synthetase (ASNS) aspartate. On the other hand, in tumor needed to be taken outside addition synthesized ASNS within because of rapid growth cells. Glioblastoma one aggressive brain tumors, and temozolomide frequently used. After glioblastoma acquire resistance temozolomide, no effective chemotherapy remained. The object this study evaluate whether metabolism, especially asparagine, could a new target treatment primary recurrent glioblastoma. Temozolomide-sensitive cell lines (U251, U87), U251- or U87 derived temozolomide-resistant were obtained after long parental used for experiments. Genetical inhibition using siRNA suppressed proliferation temozolomide-sensitive inducing apoptosis. Adding medium reversed effect targeting ASNS. L-asparaginase, converts into aspartate, reduced colonogenicity L-asparaginase increased expression mRNA ASNS, potentiated L-asparaginase-induced anti-tumor effect. For U87-derived also enhanced L-asparaginase. conclusion, will therapeutic option