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[Effect of gefitinib on radiosensitivity of gastric cancer cell lines]
Wei-Guo Cao1, Tao Ma, Jian-Fang Li
1Department of Oncology, Ruijin Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai, 200025, PR China.
Background & Objective:
Epidermal growth factor receptor (EGFR) is expressed in most human epithelial cancers and is involved in the development of cancer cell resistance to irradiation. We used gefitinib, a selective EGFR tyrosine kinase inhibitor (EGFR-TKI), to investigate its effects and mechanisms in enhancing the radiosensitivity of human gastric cancer cell lines in vitro.
Methods:
The expression of EGFR protein in 7 human gastric cell lines (MKN45, SGC7901, SNU-1, N87, AGS, SNU-16, and KATO-III) was determined by Western blot, in which 2 cell lines with high expression of EGFR were selected for additional test. The inhibitory effect of gefitinib on cell proliferation was measured by MTT assay. Cell survival was determined by clonogenic assay, and then the radiosensitivity parameters were calculated. The effects of gefitinib in combination with radiation on cell apoptosis and cell cycle distribution were analyzed by flow cytometry.
Results:
Of the 7 gastric cancer cell lines, the expression of EGFR in MKN45 and SGC7901 cells were the highest. The 50% inhibition concentrations (IC(50)) of gefitinib were 0.4 mmol/L for MKN45 cells and 0.8 mmol/L for SGC7901 cells. Cell survival was significantly decreased with the elevation of gefitinib concentration or radiation dose (P<0.05). When treated with 0.1x and 0.2 x IC(50) of gefitinib, the radiosensitization enhancement ratios (SER) of MKN45 cells were 1.102 and 1.154, and those of SGC7901 cells were 1.092 and 1.176, respectively. Either gefitinib or radiation induced cell apoptosis, reduced the percentage of cells at S phase and increased the percentage of cells at G(2)/M phase (P<0.01).
Conclusions:
Gefitinib followed by radiation could increase the radiosensitivity of MKN45 and SGC7901 cells with high expression of EGFR and inhibit cell proliferation, induce apoptosis, and alter cell phase distribution. Gefitinib could be a radiation sensitizer for gastric tumors with high expression of EGFR.
Insights
Gefitinib enhances radiation therapy effectiveness in gastric cancer cells with high EGFR expression. This EGFR inhibitor increases radiosensitivity, inhibits proliferation, and promotes apoptosis, offering a potential strategy for gastric tumor treatment.
Area of Science:
- Oncology
- Molecular Biology
- Radiotherapy Research
Background:
- Epidermal growth factor receptor (EGFR) is prevalent in epithelial cancers and contributes to radioresistance.
- Gefitinib, an EGFR tyrosine kinase inhibitor (EGFR-TKI), is investigated for its potential to overcome this resistance.
Purpose of the Study:
- To evaluate the effects of gefitinib in enhancing the radiosensitivity of human gastric cancer cell lines.
- To elucidate the mechanisms by which gefitinib impacts cancer cell proliferation, apoptosis, and cell cycle distribution in conjunction with radiation.
Main Methods:
- Western blot analysis identified EGFR expression in seven gastric cancer cell lines.
- High EGFR-expressing cell lines (MKN45, SGC7901) were treated with gefitinib and radiation.
- MTT assays, clonogenic assays, and flow cytometry assessed cell proliferation, survival, radiosensitivity, apoptosis, and cell cycle changes.
Main Results:
- Gefitinib significantly reduced cell survival and increased radiosensitization enhancement ratios (SER) in MKN45 and SGC7901 cells.
- Combined gefitinib and radiation treatment induced apoptosis and altered cell cycle distribution, increasing G2/M phase and decreasing S phase.
- The study identified specific IC50 values for gefitinib in the selected cell lines.
Conclusions:
- Gefitinib significantly enhances the radiosensitivity of gastric cancer cells with high EGFR expression.
- The combination of gefitinib and radiation inhibits proliferation, induces apoptosis, and modifies cell cycle distribution.
- Gefitinib shows promise as a radiosensitizer for EGFR-expressing gastric tumors.
