Ozensoy Guler O, Arslan O, Kockar F
Department of Chemistry, Balikesir University Science and Art Faculty, Cagis-Kampus, Balikesir, Turkey.
Methods Find Exp Clin Pharmacol. 2008 Jun;30(5):335-40. doi: 10.1358/mf.2008.30.5.1143022.
Carbonic anhydrase IX (CA IX) and, to a lesser extent, carbonic anhydrase XII (CA XII) are highly overexpressed in hypoxic tumors. In this study, the inhibitory effects of 11 different anticancer drugs including paclitaxel, amethopterin, etoposide, irinotecan, gemcitabine, 5-fluorouracil, oxaliplatin, epirubicin, cisplatin and carboplatin on the tumor-associated carbonic anhydrase isozymes CA IX and CA XII and cytosolic carbonic anhydrases I and II have been investigated. SX.18MV-R Applied Photophysics stopped-flow instrument was used for measuring the initial velocities for the CO2 hydration reaction catalyzed by different CA isozymes, by following the change in the absorbance of a pH indicator. CA IX and CA XII were the most affected by carboplatin and cisplatin amongst the panel of anticancer drugs. Moreover, the cytosolic carbonic anhydrases I and II can also be affected. Consequently, CA IX and CA XII are interesting targets for anticancer drug development, although more selective and powerful CA inhibitors could prove useful for elucidating the role of the protein in hypoxic cancers, for controlling the pH imbalance in tumor cells and for developing diagnostic or therapeutic applications for the management of hypoxic tumors, generally unresponsive to classical chemo- and radiotherapy.
碳酸酐酶IX（CA IX）以及在较小程度上的碳酸酐酶XII（CA XII）在缺氧肿瘤中高度过表达。在本研究中，已对包括紫杉醇、甲氨蝶呤、依托泊苷、伊立替康、吉西他滨、5-氟尿嘧啶、奥沙利铂、表柔比星、顺铂和卡铂在内的11种不同抗癌药物对肿瘤相关碳酸酐酶同工酶CA IX和CA XII以及胞质碳酸酐酶I和II的抑制作用进行了研究。使用SX.18MV-R Applied Photophysics停流仪，通过跟踪pH指示剂吸光度的变化来测量不同CA同工酶催化的CO2水合反应的初始速度。在抗癌药物组中，CA IX和CA XII受卡铂和顺铂的影响最大。此外，胞质碳酸酐酶I和II也会受到影响。因此，CA IX和CA XII是抗癌药物开发的有趣靶点，尽管更具选择性和强效的CA抑制剂可能有助于阐明该蛋白在缺氧癌症中的作用、控制肿瘤细胞中的pH失衡以及开发用于管理通常对经典化疗和放疗无反应的缺氧肿瘤的诊断或治疗应用。
