EGFR inhibitor enhances cisplatin sensitivity of human glioma cells.

Abstract

Epidermal growth factor receptor (EGFR) is found to express at high levels in a variety of solid tumors including gliomas. This study was to examine the effect of an EGFR-tyrosine kinase inhibitor (AG1478) alone or in combination with cisplatin (CDDP) on the growth of glioma cells (U87). U87 glioma cells were treated with AG1478 (10 μmol/L) or CDDP (25 μmol/L) as a single agent or in combination for 24 or 48 h. The expression of EGFR and the components in its downstream signaling pathway [extracellular signal-regulated kinase (ERK), protein kinase B (AKT)] in U87 glioma cells was detected by Western blotting. Cell growth, cell cycle distribution and cell apoptosis were determined by MTT method and flow cytometry, respectively. The results showed that CDDP could induce the activation of EGFR and the components in its downstream signaling pathways in a concentration-dependent manner. The combined treatment of AG1478 with CDDP could inhibit the proliferation of U87 glioma cells, arrest the cell cycle and promote cell apoptosis. In the EGFR signaling pathway, AG1478 decreased the phosphorylation of ERK, AKT and EGFR in U87 glioma cells. It was concluded that the combined treatment of AG1478 and CDDP may exert synergistic inhibitory effects on the growth of glioma cells by suppressing the activities of EGFR, AKT and ERK.

• Authors: Yan Zhang, Xihong Xing, Hongfeng Zhan, Qiaoyu Li, Yu Fan, Liping Zhan, Qiang Yu, Jian Chen
• Journal: Journal of Huazhong University of Science and Technology. Medical sciences = Hua zhong ke ji da xue xue bao. Yi xue Ying De wen ban = Huazhong keji daxue xuebao. Yixue Yingdewen ban (J Huazhong Univ Sci Technolog Med Sci) Vol. 31 Issue 6 Pg. 773-778 (Dec 2011) ISSN: 1672-0733 [Print] China
• PMID: 22173497 (Publication Type: Journal Article)

Chemical References

• Quinazolines
• Tyrphostins
• RTKI cpd
• EGFR protein, human
• ErbB Receptors
• Protein Tyrosine Phosphatases
• Cisplatin

Topics

• Apoptosis (drug effects)
• Brain Neoplasms (metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Cisplatin (pharmacology)
• Drug Resistance, Neoplasm (drug effects)
• Drug Synergism
• ErbB Receptors (antagonists & inhibitors)
• Glioma (metabolism, pathology)
• Humans
• Protein Tyrosine Phosphatases (antagonists & inhibitors)
• Quinazolines (pharmacology)
• Tyrphostins (pharmacology)