Reversal of Cisplatin Resistance by Epigallocatechin Gallate Is Mediated by Downregulation of Axl and Tyro 3 Expression in Human Lung Cancer Cells

Title
Reversal of Cisplatin Resistance by Epigallocatechin Gallate Is Mediated by Downregulation of Axl and Tyro 3 Expression in Human Lung Cancer Cells
Author(s)
이추희김경찬[김경찬]
Keywords
TUMOR-GROWTH; THERAPEUTIC TARGET; MYELOID-LEUKEMIA; CARCINOMA CELLS; P-GLYCOPROTEIN; OVARIAN-CANCER; IN-VITRO; RECEPTOR; KINASE; (-)-EPIGALLOCATECHIN-3-GALLATE
Issue Date
201402
Publisher
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY
Citation
KOREAN JOURNAL OF PHYSIOLOGY & PHARMACOLOGY, v.18, no.1, pp.61 - 66
Abstract
Lung cancer is still the number one cause of death from cancer worldwide. The clinical effect of platinum-based chemotherapy for non-small cell lung cancer is constrained by the resistance to drug. To overcome chemo-resistance, various modified treatment including combination therapy has been used, but overall survival has not been improved yet. In this study, chemo-resistant lung cancer cells, A549/Cis and H460/Cis, were developed by long-term exposure of cells to cisplatin and the proliferative capability of these resistant cells was verified to be reduced. We found cytotoxic effect of epigallocatechin gallate (EGCG), a major catechin derived from green tea, on both the parental lung cancer cells, A549 and H460, and their cisplatin resistant cells, A549/Cis and H460/Cis. ELISA and Western blot analysis revealed that EGCG was able to increase interlukine-6 (IL-6) production per cell, whereas its downstream effector Signal transducers and activators of transcription 3 (STAT3) phosphorylation was not changed by EGCG, indicating that IL-6/STAT3 axis is not the critical signaling to be inhibited by EGCG. We next found that EGCG suppresses the expression of both Axl and Tyro 3 receptor tyrosine kinases at mRNA and protein level, explaining the cytotoxic effect of EGCG on lung cancer cells, especially, regardless of cisplatin resistance. Taken together, these data suggest that EGCG impedes proliferation of lung cancer cells including their chemo-resistant variants through downregulation of Axl and Tyro 3 expression.
URI
http://hdl.handle.net/YU.REPOSITORY/33136http://dx.doi.org/10.4196/kjpp.2014.18.1.61
ISSN
1226-4512
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의과대학 > 생화학.분자생물학교실 > Articles
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