| Summary: | 碩士 === 長庚大學 === 醫學生物技術研究所 === 97 === Oral cancer (ORC) is the sixth most frequent cancer in the world with an estimated over 500,000 new cases being diagnosed annually. Oral cancer is characterized as prolonged exposure to potential risk factors, including cigarette smoking. Worldwide, approximately 80% of ORC patients have smoked or used tobacco products; and these patients are estimated with 5~7 times greater risk of developing cancer than nonsmokers. Nicotine is the most important active tobacco component. How the nicotine affects cell phenotype leading to cancer development is largely unknown. To elucidate the molecular basis of nicotine induced oral carcinogenesis and mimic clinical situation, we have established 6 sublines of oral mucosa cells, by chronic treatment with nicotine at the IC70 dose for 3 months. Results of these sublines showed higher tolerance to further nicotine treatment, with 1.2 to 2.1 fold of increase in various cell lines. Although no significant difference in radiosensitivity, these sublines exhibited higher resistance in cisplatin treatment, with approximately averaged 1.6 folds more of resistance in all cell lines. These results may imply the potential chemoresistance in the cisplatin treating ORC patients with smoking habit. As for cell growth, these nicotine-trained sublines also showed a transiently slow down in the first month but back to the same rate with the parent cells after 3 months. More significantly, the invasion and migration abilities were increased with the treatment time in all lines of cells. At the end of 3 month, the invasion ability increased to 2 to 7.5 folds among the sublines. These phenotypic alterations were accompanying with epithelial-mesenchymal transition (EMT) as indicated by the specific marker alterations. cDNA microarray was used to compare the transcriptomes between the parental and sublines. Heretical cluster and algorithmic analyses of the microarray dataset revealed that several functional pathways might associate with these phenotypic alterations. Results of this study provide cellular and molecular knowledge in the cigarette associated oral carcinogenesis.
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