| Summary: | 碩士 === 中興大學 === 生物醫學研究所 === 95 === Lung cancer is the leading cause of cancer deaths worldwide. Non-small cell lung cancer (NSCLC) accounts for about 85% of all types of lung cancer, while small cell lung cancer (SCLC) accounts for the rest 15%. In spite of continuous invention of treatments, the overall five-year survival rate remains low. Novel therapeutic strategies to improve efficacy in accord with safety are urgently needed. Gefitinib is a quinazoline derivative that selectively inhibits epithelial growth factor receptor (EGFR) tyrosine kinase activity and is under clinical use in cancer patients. Clinically, gefitinib has good antitumor activity and tolerability in Taiwan patients with advanced NSCLC. In some of patients, the unique side effect of gefitinib is skin hyperpigmentation. However, the molecular mechanism of gefitinib-mediated melanogenesis effect is not fully understood. In this study, the effect of gefitinib on melanogenesis was examined in murine B16F1 and human A2058 melanoma cells. The tyrosinase activity was apparently elevated in cells treated with gefitinib. Moreover, treatment with gefitinib increased the melanin content of melanoma cells in a dose- and time-dependent manner. In studies of the mechanisms underlying such induction, we found that the molecular promoting pigment production such as tyrosinase, tyrosinase-related protein 1 and 2 were increasingly expressed in gefitinib-treated melanoma cells, which was accompanied by the inactivation of Akt and ERK, two factors documented to exert inhibitory effect on melanogenesis. Taken together, our findings propose that gefitinib induces melanin synthesis through the inactivation of negative regulators of pigment generation and subsequent elevation of melanin-producing enzymes.
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