Tsochantaridis Ilias, Roupas Angelos, Voulgaridou Georgia-Persephoni, Giatromanolaki Alexandra, Koukourakis Michael I, Panayiotidis Mihalis I, Pappa Aglaia
Department of Molecular Biology & Genetics, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Department of Pathology, University General Hospital of Alexandroupolis, Democritus University of Thrace, 68100 Alexandroupolis, Greece.
Biomedicines. 2021 Jan 6;9(1):44. doi: 10.3390/biomedicines9010044.
Aldehyde dehydrogenases (ALDHs) are NAD(P)-dependent enzymes that catalyze the oxidation of endogenous and exogenous aldehydes to their corresponding carboxylic acids. ALDHs participate in a variety of cellular mechanisms, such as metabolism, cell proliferation and apoptosis, as well as differentiation and stemness. Over the last few years, ALDHs have emerged as cancer stem cell markers in a wide spectrum of solid tumors and hematological malignancies. In this study, the pathophysiological role of ALDH1B1 in human colorectal adenocarcinoma was investigated. Human colon cancer HT29 cells were stably transfected either with human green fluorescent protein (GFP)-tagged ALDH1B1 or with an empty lentiviral expression vector. The overexpression of ALDH1B1 was correlated with altered cell morphology, decreased proliferation rate and reduced clonogenic efficiency. Additionally, ALDH1B1 triggered a G2/M arrest at 24 h post-cell synchronization, probably through p53 and p21 upregulation. Furthermore, ALDH1B1-overexpressing HT29 cells exhibited enhanced resistance against doxorubicin, fluorouracil (5-FU) and etoposide. Finally, ALDH1B1 induced increased migratory potential and displayed epithelial-mesenchymal transition (EMT) through the upregulation of and and the consequent downregulation of Taken together, ALDH1B1 confers alterations in the cell morphology, cell cycle progression and gene expression, accompanied by significant changes in the chemosensitivity and migratory potential of HT29 cells, underlying its potential significance in cancer progression.
醛脱氢酶（ALDHs）是一类依赖NAD(P)的酶，可催化内源性和外源性醛氧化为相应的羧酸。ALDHs参与多种细胞机制，如代谢、细胞增殖和凋亡，以及分化和干性维持。在过去几年中，ALDHs已成为多种实体瘤和血液系统恶性肿瘤中癌症干细胞的标志物。在本研究中，我们探究了ALDH1B1在人类结肠腺癌中的病理生理作用。人结肠癌HT29细胞分别用携带人绿色荧光蛋白（GFP）标记的ALDH1B1的慢病毒载体或空慢病毒表达载体进行稳定转染。ALDH1B1的过表达与细胞形态改变、增殖速率降低和克隆形成效率降低相关。此外，在细胞同步化后24小时，ALDH1B1可能通过上调p53和p21引发G2/M期阻滞。此外，过表达ALDH1B1的HT29细胞对阿霉素、氟尿嘧啶（5-FU）和依托泊苷表现出更强的抗性。最后，ALDH1B1通过上调 和 并随后下调 诱导迁移潜能增加并表现出上皮-间质转化（EMT）。综上所述，ALDH1B1导致细胞形态、细胞周期进程和基因表达发生改变，同时HT29细胞的化学敏感性和迁移潜能也发生显著变化，这表明其在癌症进展中具有潜在重要意义。
