Growth suppression of glioblastoma multiforme cell line response to the combination of Temozolomide and Nimotuzumab

Abstract

Background: Researches towards Glioblastoma multiforme therapy (GBM) has been performed, especially in finding the tumor’s genetic cellular expression. The overexpression of EGFR, frequently found in human malignancies, is known to significantly impact cancer cells hallmark traits, such as increased cell survival, proliferation and invasion. This research is performed to figure out the synergistic effect of temozolomide, the main chemotherapy regimen used, and the monoclonal antibody anti-EGFR nimotuzumab in inhibiting the growth of GBM cells in vitro. Methods: We performed cell cultures using GBM U87MG cells and administered nimotuzumab 1000µg/ml and temozolomide 20 µg/ml in different sequences and timings. Inhibition of GBM cell growth is evaluated by measuring Ki-67 and γH2AX levels using flowcytometry and tested with one-way ANOVA. Data were analyzed using SPSS version 21 for Windows. Results: Levels of Ki-67 were in the control group (23.17±1.72), nimotuzumab monotherapy (15.43±1.70), temozolomide monotherapy (14.80±1.37), simultaneous therapy (10.73±1.19), nimotuzumab 24 hours before temozolomide (10.57±1.05), and nimotuzumab 48 hours before temozolomide (14.47±1.37). The level of γH2AX is measured in the control group (11.90±1.25), nimotuzumab monotherapy (29.33±1.91), temozolomide monotherapy (28.13±1.58), simultaneous therapy (41.53±3.51), nimotuzumab 24 hours before temozolomide (39.56±2.06), and nimotuzumab 48 hours before temozolomide (35.93±3.56). Conclusion: This research shows that administration of nimotuzumab simultaneously with temozolomide and nimotuzumab 24 hours before temozolomide effectively inhibits the growth of U87MG GBM cells. Inhibition of EGFR expression before temozolomide administration is able to increase DNA damage and inhibit the proliferation of glioma cells.