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

Title
The enhanced tumor inhibitory effects of gefitinib and L-ascorbic acid combination therapy in non-small cell lung cancer cells
Authors
Lee, Kyoung EunHahm, EunsilBae, SeyeonKang, Jae SeungLee, Wang Jae
Ewha Authors
이경은
SCOPUS Author ID
이경은scopus
Issue Date
2017
Journal Title
ONCOLOGY LETTERS
ISSN
1792-1074JCR Link1792-1082JCR Link
Citation
vol. 14, no. 1, pp. 276 - 282
Keywords
L-ascorbic acidgefitinibvitamin Cnon-small cell lung carcinomaepidermal growth factor receptor
Publisher
SPANDIDOS PUBL LTD
Indexed
SCIE; SCOPUS WOS
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 (R)) in lung cancer cell lines. A total of three human lung cancer cell lines were used. The antipro-liferative 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 similar to 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.
DOI
10.3892/ol.2017.6109
Appears in Collections:
의과대학 > 의학과 > Journal papers
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