The enhanced tumor inhibitory effects of gefitinib and L‑ascorbic acid combination therapy in non‑small cell lung cancer cells

Lee,Kyoung Eun; Hahm,Eunsil; Bae,Seyeon; Kang,Jae Seung; Lee,Wang Jae

doi:10.3892/ol.2017.6109

The enhanced tumor inhibitory effects of gefitinib and L‑ascorbic acid combination therapy in non‑small cell lung cancer cells

Authors:
- Kyoung Eun Lee
- Eunsil Hahm
- Seyeon Bae
- Jae Seung Kang
- Wang Jae Lee
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Affiliations: Division of Hematology‑Oncology, Department of Internal Medicine, School of Medicine, Ewha Womans University, Seoul 07985, Republic of Korea, Department of Anatomy and Tumor Immunity Medical Research Center, College of Medicine, Seoul National University, Seoul 03080, Republic of Korea
Published online on: May 2, 2017 https://doi.org/10.3892/ol.2017.6109
Pages: 276-282

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Abstract

Despite documentation of successful therapy with epidermal growth factor receptor (EGFR) tyrosine kinase inhibitors in patients with lung cancer, the response rate of patients treated with this therapy remains low. The present study investigated whether L‑ascorbic acid serves an adjuvant role in vitro when combined with the EGFR tyrosine kinase inhibitor gefitinib (Iressa®) in lung cancer cell lines. A total of three human lung cancer cell lines were used. The antiproliferative effects and changes in the cell cycle and expression of intracellular signaling molecules, including extracellular signal‑regulated kinases (Erk), signal transducer and activator of transcription 3 (Stat3) and protein kinase B (Akt), were measured in cells treated with gefitinib and/or L‑ascorbic acid at various concentrations. When combined with gefitinib, L‑ascorbic acid exhibited an additive effect on cell proliferation in all gefitinib‑sensitive and gefitinib‑resistant cell lines. A decrement of ~40% was observed with a low dose 0.5 mM L‑ascorbic acid and gefitinib in the relatively gefitinib‑resistant A549 cell line (85.6±5.4% with gefitinib alone vs. 52.7±7.3% with combination therapy; P=0.046). The downregulation of intracellular signaling cascades, including EGFR, Akt, Erk and Stat3, was also observed. L‑Ascorbic acid serves an adjuvant role when administered in combination with gefitinib; however, the degree of inhibition of cell proliferation differs between lung cancer cell lines.

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