Epidermal growth factor induction of resistance to topoisomerase II toxins in human squamous carcinoma A431 cells
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AbstractAlteration of the epidermal growth factor (EGF) signaling pathway occurs frequently in human cancer cells and may subsequently affect the cell survival towards anticancer agents. To elucidate the effect of long-term EGF treatment on the chemo-sensitivity of human cancer cells, human squamous carcinoma A431 cells (AP) were incubated continuously with 50 ng/ml EGF for 30 weeks and these cells were designated as the AC cells. The long-term EGF treatment did not alter the EGFR level and the EGF-induced protein tyrosine phosphorylation pattern in the AC cells. By MTT assay, the AC cells were shown to be more resistant than the AP cells to doxorubicin, etoposide and amsacrine but not to cisplatin. Among the drug-resistant proteins, topoisomerase II alpha (topoII) was downregulated in the AC cells while there was no apparent change in the levels of P-glycoprotein, MRP-1 or glutathione- S-transferase-pi as compared to the AP cells. Furthermore, knockdown of topoII by antisense topoII oligonucleotide transfection decreased the sensitivity to doxorubicin, etoposide and amsacrine in the A431 cells. Results from the present study support an idea that long-term treatment with EGF may induce drug resistance in cells through the downregulation of topoII.
All Author(s) ListTsang WP, Kong SK, Kwok TT
Journal nameOncology Reports
Volume Number16
Issue Number4
Pages789 - 793
LanguagesEnglish-United Kingdom
KeywordsA431 cells; epidermal growth factor; topoisomerase
Web of Science Subject CategoriesOncology; ONCOLOGY

Last updated on 2021-27-02 at 00:51