酒精（乙醇）在人體內的分解代謝，主要經由氧化途徑完成，參與的酶系統包括醇脫氫酶（ADH）、醛脫氫酶（ALDH）、過氧化氫酶（catalase）和微粒體乙醇氧化系統（MEOS）。ADH與ALDH組成因種族差異而不同，其表現及分佈亦因組織而異，因而影響不同族群個體的飲酒行為，以及在體內不同部位的乙醇代謝效應，進而影響組織器官傷害的發生。乙醇會抑制細胞生長與影響細胞正常的生理功能，促使細胞走向凋亡的路徑，而乙醇代謝產物乙醛則是具有細胞毒性與致癌性，乙醛可與DNA共價結合形成加成產物誘發基因突變。本研究目的為以人類口腔癌細胞（OECM-1）以及人類正常口腔細胞（NHOK）為實驗對象，探討經乙醇處理後，乙醇及其代謝物產生的氧化壓力，所造成的細胞凋亡效應。經過實驗驗後，乙醇的確會引發OEC-M1進行細胞凋亡，在進一步的探討後，發現乙醇的代謝物：乙醛，有較強引發細胞凋亡的作用。當我們分別口腔癌細胞株與正常口腔初代培養的細胞（NHOK）來比較時，OEC-M1具有抗性，因此有較低比例的細胞進行細胞凋亡反應。另外，根據文獻最近被發現的一個新的蛋白分解酶：matriptase，參與許多的癌病變，包含：乳癌、卵巢癌、前列腺癌、肺癌、大腸癌、腎癌以及口腔癌等，當癌症越末期，matriptase表達的量越高，也有越多的matriptase被活化。因此，我們進一步來觀察乙醇對matriptase的影響，我們發現matriptase會被乙醇活化，matriptase可能是乙醇引發癌病變的另一個可能的路徑。

Several enzymes are involved in ethanol metabolism. Whereas alcohol dehydrogenase (ADH) metabolizes the bulk of ethanol in the liver, other enzymes, such as cytochrome P4502E1 and catalase, also contributes to the production of acetaldehyde from ethanol oxidation. Futhermore, acetaldehyde can be metabolized to form acetate by aldehyde dehydrogenase (ALDH). In humans, genetic polymorphisms of enzymes ethanol dehydrogenase (ADH) and aldehyde dehydrogenase (ALDH) are also associated with ethanol habits. Ethanol consumption increase apoptosis of cell, and human body. Acetaldehyde promotes adducts formation, as well as DNA damage, which promotes mutagenesis. Apoptosis is an active, tightly regulated, cell death program that enables organisms to actively eliminate damaged, senescent, or unwanted cells during embryogenesis, maturation of immune system, and adult tissue turnover. In this study, we utilized oral cells to learn the possible tumorigenesis mechanism in oral cancer. When oral cancer cell line (OEC-M1) were treated with ethanol, we did observe increased apoptosis ratio. When OEC-M1 cells were treated with ALDH inhibitor, acetaldehyde was increased. Therefore acetaldehyde can trigger stronger apoptosis signal. When we further study the mechanism, we found ROS (reactive oxygen species) could play the crucial role to regulate ethanol-induced apoptosis. Sine OEC-M1 is a cancer cell line, OEC-M1 shows stronger resistance than NHOK (normal human oral keratinocyte) cells. Recent studies have shown matriptase, a novel protease, could be important in different cancers: breast cancer, ovarian cancer, prostate cancer, lung cancer, colon cancer, kidney cancer, and oral cancer. For late stage ceancers, matriptase expression is increased and the activation is increased as well. Thus, we tried to moniter the activation of matriptase when cells were treated with ethanol. We found ethanol did activate matriptase in OEC-M1. Matriptase activation could be another mechanism to trigger tumorigenesis in oral cancer.

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