Paškevičiūtė Miglė, Petrikaitė Vilma
Laboratory of Drug Targets Histopathology, Institute of Cardiology, Lithuanian University of Health Sciences Kaunas, Lithuania.
Institute of Physiology and Pharmacology, Faculty of Medicine, Lithuanian University of Health Sciences Kaunas, Lithuania.
Am J Cancer Res. 2020 Jun 1;10(6):1761-1769. eCollection 2020.
The aim of our study was to assess the influence of two carbonic anhydrase (CA) inhibitors (methazolamide (MTZ)) and U-104 on weakly basic anticancer drug doxorubicin (DOX) and pegylated liposomal doxorubicin (PLD) delivery into monolayer-cultured 4T1 murine breast cancer cells (2D cultures) and tumor spheroids (3D cultures) at pH 6.0 and 7.4. The effect of compounds on cell viability was evaluated by MTT assay. Spheroids were formed using 3D Bioprinting method. The penetration of DOX and PLD into cells and spheroids was evaluated using fluorescence microscopy. Both MTZ and U-104 increased the DOX (5 µM) and PLD (concentration corresponding to 5 µM DOX) penetration into monolayer-cultured cells at acidic conditions but did not enhance drug delivery at physiological pH. Pretreatment with U-104 inhibitors also increased DOX and PLD delivery into tumor spheroids. Thus, U-104 may be worthy of further studies as possible transport modulator of weakly basic drugs.
我们研究的目的是评估两种碳酸酐酶（CA）抑制剂（甲醋唑胺（MTZ））和U-104在pH 6.0和7.4条件下，对弱碱性抗癌药物阿霉素（DOX）和聚乙二醇化脂质体阿霉素（PLD）进入单层培养的4T1小鼠乳腺癌细胞（二维培养）和肿瘤球体（三维培养）的影响。通过MTT法评估化合物对细胞活力的影响。使用3D生物打印方法形成球体。使用荧光显微镜评估DOX和PLD进入细胞和球体的渗透情况。MTZ和U-104在酸性条件下均增加了DOX（5 μM）和PLD（对应于5 μM DOX的浓度）进入单层培养细胞的渗透率，但在生理pH值下未增强药物递送。用U-104抑制剂预处理也增加了DOX和PLD进入肿瘤球体的递送。因此，U-104作为弱碱性药物可能的转运调节剂值得进一步研究。
