RESUMEN
Renal fibroblast proliferation is key in renal fibrosis and chronic kidney disease. Transforming growth factor-ß1 (TGF-ß1) has been demonstrated to be an important factor that induces cell proliferation in renal fibroblasts. Epidermal growth factor receptor (EGFR) is also recognized as a factor promoting renal fibroblast proliferation. In addition, mitogenactivated protein kinase signaling pathways are associated with TGFß1 and EGFRinduced cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, is predominantly used as an antitumor therapeutic agent in clinical therapeutic strategies. However, gefitinib has been suggested to exert antiproliferative effects on renal fibroblasts, however, highdose gefitinib may result in serious side effects. The present study aims to determine whether lowdose gefitinib reduces gefitinibinduced side effects and maintains the antiproliferative effects on renal fibroblasts. TGFß1 promotes cell proliferation in renal fibroblasts, and the current study demonstrates that lowdose gefitinib treatment exhibits antiproliferative effects similar to those of highdose gefitinib treatment. Thus, although highdose gefitinib is a conventional antitumor drug, lowdose gefitinib may be of use in renal fibrosis treatment. Furthermore, the present study demonstrates that a combined treatment with low-dose gefitinib and vitamin E has synergistic effects that reduce TGFß1induced fibroblast proliferation, cell-cycle arrest and the ERK phosphorylation pathway.