| Summary: | 碩士 === 國立嘉義大學 === 生化科技學系研究所 === 98 === Emodin is a natural anthraquinone derivative that exists in several plants and has been reported to show anti-tumor efficacy on cancer and enhance chemosensitivity. Polyphenolic compound resveratrol also has been shown many beneficial properties including against cardiovascular disease and anti-cancer effect. Gefitinib (IressaR) is a selective epidermal growth factor receptor (EGFR) tyrosine kinase inhibitor for human non-small cell lung cancer (NSCLC). The main objective of this thesis is to study the mechanism of gefitinib-induced cytotoxicity enhanced by emodin and resveratrol in human lung cancer cells. Overexpression of Rad51 or ERCC1 in lung cancer has been shown to resistance to DNA damage inducing cancer therapies. To decrease Rad51 and ERCC1 expression in lung cancer could reduce the ability of resistance to cancer therapy. In this study, the combination of emodin and gefitinib decreased phospho-ERK1/2 and Rad51 protein levels, and resveratrol enhanced the effect of gefitinib down-regulated ERCC1 protein expression. However, Low dose (2-10 M) of emodin and resveratrol did not affect the cell viability and expression of Rad51 and ERCC1, respectively. The combination of emodin or resveratrol and gefitinib elevated the population of sub-G1 which was associated with apoptosis in NSCLC cells. But resveratrol is the main effective factor to cause NSCLC cells arrest in S phase as talk to the combination has the effect on cell cycle. According to the study, emodin or resveratrol and gefitinib combined treatment may be basis of a novel and better therapeutic modality for advanced lung cancer.
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