Download

Download Full Text (1.2 MB)

Presentation date

Summer 8-8-2024

College, Institute, or Department

Internal Medicine (SURP)

Faculty Mentor

Dr. Nicole Shonka

Research Mentor

Dr. Raghupathy Vengoji

Abstract

Glioblastoma is an aggressive malignant brain cancer with a dismal 5-year survival rate of 6.9%. Despite current treatments – surgical resection, radiation, and chemotherapy – GBM remains incurable, highlighting the urgent need for more effective targeted therapies. Nerve Growth Factor Receptor (NGFR) plays a key role in the maintenance and growth of gliomas and is upregulated during GBM progression. Tyrphostin (AG-879), an inhibitor of TrkA in the NGFR pathway, was investigated in this study. We hypothesized that NGFR contributes to GBM progression by promoting proliferation and its pharmacological targeting will inhibit GBM growth. The objective was to determine the impact of AG-879 on cell proliferation and elucidate the underlying mechanisms of its anti-GBM effects. To evaluate this, U118 GBM cells were split into control and treatment (10µM AG-879) groups and allowed to incubate for 72-hours at 37.5oC. Afterwards, cell lysate was collected, and Lowry protein estimation was performed. Western Blot analysis was conducted, and membranes were probed with antibodies that targeted β-actin (loading control), phospho-AKT (proliferation marker), and total AKT. Our results demonstrated that AG-879 effectively decreases U118 cell proliferation by inhibiting AKT activation (phospho-AKT) at 10µM. Future studies should evaluate the effect of AG-879 on markers of apoptosis and cell cycle arrest.

Keywords

Glioblastoma (GBM), NGFR, Tyrphostin (AG-879), phospho-AKT

Tyrphostin (AG-879) Decreases AKT Activation Through NGFR Inhibition in Human Glioblastoma Cell Lines

Share

COinS