Pidkovka Nataliya, Rachkevych Olena, Belkhiri Abbes
Department of Health Science, South College, Nashville, TN, USA.
Department of Obstetrics and Gynecology, Danylo Halytsky Lviv National Medical University, Lviv, Ukraine.
Oncotarget. 2021 Feb 16;12(4):379-391. doi: 10.18632/oncotarget.27893.
Cytochrome P450 (CYP) epoxygenases, a multi-gene superfamily of heme-containing enzymes, are commonly known to metabolize endogenous arachidonic acid (AA) to epoxyeicosatrienoic acids (EETs). The role of CYPs is mostly studied in liver drugs metabolism, cardiac pathophysiology, and hypertension fields. Particularly, the biological functions of these enzymes have increasingly attracted a growing interest in cancer biology. Most published studies on CYPs in cancer have been limited to their role as drug metabolizing systems. The activity of these enzymes may affect drug pharmacokinetics and bioavailability as well as exogenous compounds turnover. Some CYP isoforms are selectively highly expressed in tumors, suggesting a potential mechanistic role in promoting resistance to chemotherapy. Majority of drugs elicit their effects in extrahepatic tissues whereby their metabolism can significantly determine treatment outcome. Nonetheless, the role of extrahepatic CYPs is not fully understood and targeting these enzymes as effective anti-cancer therapies are yet to be developed. This review article summarizes an up-to-date body of information from published studies on CYP enzymes expression levels and pathophysiological functions in human normal and malignant gastrointestinal (GI) tract tissues. Specifically, we reviewed and discussed the current research initiatives by emphasizing on the clinical significance and the pathological implication of CYPs in GI malignancies of esophagus, stomach, and colon.
细胞色素P450（CYP）环氧合酶是一个含血红素酶的多基因超家族，通常已知其可将内源性花生四烯酸（AA）代谢为环氧二十碳三烯酸（EETs）。CYP的作用主要在肝脏药物代谢、心脏病理生理学和高血压领域进行研究。特别是，这些酶的生物学功能在癌症生物学中越来越受到关注。大多数已发表的关于癌症中CYP的研究都局限于它们作为药物代谢系统的作用。这些酶的活性可能会影响药物的药代动力学和生物利用度以及外源性化合物的周转。一些CYP同工型在肿瘤中选择性高表达，提示其在促进化疗耐药性方面可能具有潜在的机制作用。大多数药物在肝外组织发挥作用，因此它们的代谢可显著决定治疗结果。然而，肝外CYP的作用尚未完全了解，将这些酶作为有效的抗癌疗法的研究尚未开展。这篇综述文章总结了已发表研究中关于CYP酶在人类正常和恶性胃肠道（GI）组织中的表达水平及病理生理功能的最新信息。具体而言，我们通过强调CYP在食管、胃和结肠等胃肠道恶性肿瘤中的临床意义和病理意义，对当前的研究进展进行了综述和讨论。
