Resveratrol Decreases the Resistance of Lung Cancer Cells to EGFR Tyrosine Kinase Inhibitor

• Main Authors: Chu-Ying Peng, 彭竺英
• Other Authors: Jen-Liang Su
• Format: Others
• Language: en_US
• Published: 2010
• Online Access: http://ndltd.ncl.edu.tw/handle/16102696077040719384

碩士 === 中國醫藥大學 === 癌症生物學研究所 === 98 === Lung cancer is one of the most common malignancies in many countries, including Taiwan, and also is the first leading cause of cancer-induced death. EGFR (epidermal growth factor receptor) regulated a lot of biological functions of cells including proliferation, differentiation, motility and metabolism; its overexpression or activate mutation are associated with a number of cancers. Gefitinib (Iressa), a specific EGFR tyrosine kinase inhibitor, has been used in treatment of non-small lung cancer patients. However, its therapeutic activity is limited by the development of drug resistance. Resveratrol (trans-3, 4’, 5-trihydroxystilbene) is a polyphenolic compound found in various plants and some Chinese herbs. Resveratrol has the ability to inhibit cancer formation at initiation, promotion and progression; also it has been shown to receive chemosensitive and chemopreventive effects in different experimental systems. To define the effects of resveratrol on target therapy of lung cancer cells, we used Iressa-resistance (PC-9/IR) lung cancer cells as our experimental models. In the functional assay, we found that pre-treatment with non-toxic dosages of resveratrol (1.25, 2.5, 5, 10 μM) sensitized the toxic effect of Iressa (2.5 μM) in Iressa-resistant PC-9/IR cells. Treatment with Iressa for 48 hrs induced 55.37% ± 0.37% cell death in PC-9/WT cells, but only 8.76% ± 1.56% in PC-9/IR cells. Pre-treatment with resveratrol increased Iressa-induced cell death in PC-9/IR cells (8.76% ± 1.56% cell death in vehicle + Iressa group; 48.71% ± 3.12% cell death in resveratrol + Iressa group). These results indicate that resveratrol may sensitize EGFR tyrosine kinase inhibitor in resistant lung cancer cells. To further evaluate the molecular mechanisms, we define the potential down-stream targets, such as epithelial-mesechymal transition (EMT)-related proteins and microRNAs, involved in resveratrol-induced de-resistance of EGFR tyrosine kinase inhibitor in lung cancer cells. By two-dimensional gel electrophoresis and microRNA microarray assay, we found some potential downstream targets which may involve in the resistance of lung cancer cells to EGFR tyrosine kinase inhibitor.