Combined treatment with vitamin E and gefitinib has synergistic effects to inhibit TGF-β1-induced renal fibroblast proliferation.
Renal fibroblast proliferation is key in renal fibrosis and chronic kidney disease. Transforming growth factor-β1 (TGF-β1) 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, mitogen‑activated protein kinase signaling pathways are associated with TGF‑β1‑ and EGFR‑induced cell proliferation. Gefitinib, an EGFR tyrosine kinase inhibitor, is predominantly used as an anti‑tumor therapeutic agent in clinical therapeutic strategies. However, gefitinib has been suggested to exert anti‑proliferative effects on renal fibroblasts, however, high‑dose gefitinib may result in serious side effects. The present study aims to determine whether low‑dose gefitinib reduces gefitinib‑induced side effects and maintains the anti‑proliferative effects on renal fibroblasts. TGF‑β1 promotes cell proliferation in renal fibroblasts, and the current study demonstrates that low‑dose gefitinib treatment exhibits anti‑proliferative effects similar to those of high‑dose gefitinib treatment. Thus, although high‑dose gefitinib is a conventional anti‑tumor drug, low‑dose 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 TGF‑β1‑induced fibroblast proliferation, cell-cycle arrest and the ERK phosphorylation pathway.
Department of Emergency Medicine, Taipei Tzu Chi Hospital, Buddhist Tzu Chi Medical Foundation, New Taipei 23142, Taiwan, R.O.C.
Giou-Teng
GT
Yiang
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Jen-Ni
JN
Chen
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Pei-Shiuan
PS
Lin
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Hsiao-Chun
HC
Liu
Department of Nursing, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Shu-Ying
SY
Chen
Department of Nutrition, Master Program of Biomedical Nutrition, Hungkuang University, Taichung 43302, Taiwan, R.O.C.
Chyou-Wei
CW
Wei
D000818:Animals; D002460:Cell Line; D049109:Cell Proliferation / Q000187:drug effects*; D004357:Drug Synergism; D005347:Fibroblasts / Q000166:cytology / Q000378:metabolism*; D000077156:Gefitinib; D005786:Gene Expression Regulation / Q000187:drug effects*; D007668:Kidney / Q000166:cytology / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects; D011799:Quinazolines / Q000819:agonists / Q000494:pharmacology*; D051381:Rats; D053773:Transforming Growth Factor beta1 / Q000096:biosynthesis*; D014810:Vitamin E / Q000819:agonists / Q000494:pharmacology*
D011799:Quinazolines; C508962:Tgfb1 protein, rat; D053773:Transforming Growth Factor beta1; D014810:Vitamin E; D000077156:Gefitinib