Antiangiogenic and anitumor effects of a protein kinase C beta inhibitor in human T98G glioblastoma multiforme xenografts

Although rare, the morbidity and mortality from brain tumors are significan t, Chemotherapy has made only a small impact on these tumors. The human T98 G glioblastoma multiforme cell. hue was used as a brain tumor model. The pr otein kinase Cp inhibitor 317615 . 2HCl was not highly cytotoxic toward T98 G cells in culture and was additive in cytotoxicity with carmustine (BCNU). When nude mice bearing s.c. T98G tumors were treated with 317615 . 2HCl p. o. twice daily on days 14-30 after tumor cell implantation, the number of i ntratumoral vessels stained by CD31 was decreased to 37% of control, and th e number of intratumoral vessels stained by CD105 was decreased to 50% of c ontrol. The compound 317615 . 2HCl was an active antitumor agent against s. c. growing T98G xenografts. A treatment regimen administering 317615 . 2HCl before, during, and after BCNU was compared with a treatment regimen admin istering 317615 . 2HCl sequentially after BCNU, In the tumor growth delay d etermination of the s.c. tumor, the sequential treatment regimen was more e ffective than the simultaneous treatment regimen. However, when the same tr eatments were administered to animals bearing intracranial T98G tumors, til e survival of animals receiving the simultaneous treatment regimen increase d from 41 days for those treated with BCNU alone to 102 days for animals tr eated with the combination, whereas animals receiving the sequential treatm ent regimen survived 74 days. Treatment with the protein kinase CB inhibito r decreased T98G glioblastoma multiforme angiogenesis and improved treatmen t outcome with BCNU.