2018-2019 Grant in Aid of Research
The Effects of Novel Dihydropyridine Derivatives as Anti-invasive Drugs on Glioblastoma
Tendai Hunyenyiwa
Glioblastoma (GBM) is one of the deadliest brain cancers, characterized by profuse proliferation and invasion. Glioblastoma targets astrocytes in the brain, which are glial cells involved in supplying nutrients to the brain cells among other functions. During invasion, single cancerous astrocytes migrate from the primary tumor to other parts of the brain and attach themselves to the brain tissue, starting minor tumors. The most common approach in combating glioblastoma involves surgical removal of the primary tumor, followed by radiotherapy then finally treatment with temozolomide (TMZ), a chemotherapy drug; but this treatment regimen can only earn two years or less for most patients because of invasion which makes GMB a difficult disease to treat. There is the need for developing drugs that can combat glioblastoma at the invasion stage to prevent the risk of tumor recurrence. In this proposed research, I will develop novel dihydropyridines derivatives, and investigate their effectiveness as anti-invasion agents. I will use the U87 GBM cancer cell line to test the effects of the developed drugs on cell viability; and I will also test the effects of these drugs on the expression of proteins that are highly expressed in invasive cells (MMP-2, MMP-9, ADAM 12 and ADAM 17) using western blotting. I will also run an invasion assay to compare the invasiveness of treated and untreated cells. I expect to see the reduction in cell growth and proliferation, low protein expression and limited to no invasion of cells in the invasion assay for the cells treated with the developed drugs, which will indicate the efficacy of developed compounds in reducing invasion.