Bladder cancer (BC) is the eighth most common cause of cancer death in the United States of America. BC is classified into non-muscle-invasive bladder cancer (NMIBC) and muscle-invasive bladder cancer (MIBC). Genetically, MIBCs are categorized into the more aggressive basal subtype or less aggressive luminal subtype. All-trans retinoic acid (tretinoin), the ligand for the RAR-RXR retinoic acid receptor, is clinically used as a differentiation therapy in hematological malignancies. This study aims to determine the effects of retinoic acid on arsenite-transformed malignant urothelial cells (UROtsa As), serving as a model for basal muscle-invasive bladder cancer. We treated three independent isolates of arsenite-transformed malignant human urothelial UROtsa cells (UROtsa As) with tretinoin for 48 h. Cell viability, proliferation, and apoptosis were analyzed using crystal violet staining and flow cytometry. mRNA and protein level analyses were performed using RT-qPCR and the Simple Western™ platform, respectively. Tretinoin was found to reduce cell proliferation and urosphere formation, as well as decrease the expression of basal markers (KRT1, KRT5, KRT6, EGFR) and increase the expression of luminal differentiation markers (GATA3, FOXA1). Mechanistically, the antiproliferative effect of tretinoin was attributed to the downregulation of c-myc. Our results suggest that targeting the retinoic acid pathway can diminish the aggressive behavior of basal muscle-invasive urothelial cancer and may enhance patient survival.
膀胱癌是美国第八大常见癌症致死原因。该疾病可分为非肌层浸润性膀胱癌和肌层浸润性膀胱癌。从遗传学角度，肌层浸润性膀胱癌可进一步分为侵袭性较强的基底亚型与侵袭性较低的管腔亚型。全反式维甲酸作为RAR-RXR维甲酸受体的配体，临床上已用于血液系统恶性肿瘤的分化治疗。本研究旨在探讨维甲酸对亚砷酸盐转化恶性尿路上皮细胞（UROtsa As）的作用机制，该细胞系可作为基底型肌层浸润性膀胱癌的研究模型。我们使用维甲酸处理三组独立的亚砷酸盐转化人尿路上皮UROtsa恶性细胞系48小时，通过结晶紫染色和流式细胞术分析细胞活力、增殖及凋亡情况，并分别采用RT-qPCR和Simple Western™平台进行mRNA及蛋白水平检测。研究发现维甲酸能抑制细胞增殖和尿路上皮球体形成，下调基底标志物（KRT1、KRT5、KRT6、EGFR）表达，同时上调管腔分化标志物（GATA3、FOXA1）表达。机制研究表明，维甲酸的抗增殖效应源于其对c-myc基因的下调作用。本研究成果提示，靶向维甲酸通路可降低基底型肌层浸润性尿路上皮癌的侵袭性，有望改善患者生存预后。
肿瘤(癌症)患者之家