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EGFR inhibitor enhances cisplatin sensitivity of human glioma cells
Yan Zhang1,2, Xihong Xing3, Hongfeng Zhan4
1Department of Neurosurgery, the Affiliated People's Hospital of Jiangsu University, Zhenjiang, 212002, China.
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.
Insights
This study investigated the combination of an EGFR-tyrosine kinase inhibitor (AG1478) and cisplatin (CDDP) for glioma treatment. Combined therapy effectively inhibited glioma cell growth, arrested the cell cycle, and induced apoptosis by targeting the EGFR pathway.
Area of Science:
- Oncology
- Molecular Biology
- Cancer Research
Background:
- Epidermal growth factor receptor (EGFR) is frequently overexpressed in gliomas, making it a potential therapeutic target.
- Understanding EGFR signaling pathways is crucial for developing effective glioma treatments.
Purpose of the Study:
- To evaluate the efficacy of an EGFR-tyrosine kinase inhibitor (AG1478) alone and in combination with cisplatin (CDDP) against U87 glioma cells.
- To investigate the impact of this combination therapy on EGFR downstream signaling pathways, cell proliferation, cell cycle, and apoptosis.
Main Methods:
- U87 glioma cells were treated with AG1478 and/or CDDP.
- Western blotting was used to detect EGFR, ERK, and AKT expression and phosphorylation.
- MTT assay and flow cytometry were employed to assess cell growth, cell cycle distribution, and apoptosis.
Main Results:
- Cisplatin (CDDP) treatment led to a concentration-dependent activation of EGFR and its downstream pathways (ERK, AKT).
- The combination of AG1478 and CDDP significantly inhibited U87 glioma cell proliferation.
- Combined treatment resulted in cell cycle arrest and increased apoptosis, with decreased phosphorylation of EGFR, ERK, and AKT.
Conclusions:
- AG1478 in combination with CDDP demonstrates synergistic inhibitory effects on glioma cell growth.
- The combination therapy functions by suppressing the activity of the EGFR signaling pathway, including EGFR, AKT, and ERK.
- This combination holds promise for enhancing glioma treatment strategies.
