Gumulec Jaromir, Fojtu Michaela, Raudenska Martina, Sztalmachova Marketa, Skotakova Anna, Vlachova Jana, Skalickova Sylvie, Nejdl Lukas, Kopel Pavel, Knopfova Lucia, Adam Vojtech, Kizek Rene, Stiborova Marie, Babula Petr, Masarik Michal
Department of Pathological Physiology, Faculty of Medicine, Masaryk University, Kamenice 5, CZ-62500 Brno, Czech Republic.
Central European Institute of Technology, Brno University of Technology, Technicka 3058/10, CZ-61600 Brno, Czech Republic.
Int J Mol Sci. 2014 Dec 11;15(12):22960-77. doi: 10.3390/ijms151222960.
Doxorubicin is an effective chemotherapeutic drug, however, its toxicity is a significant limitation in therapy. Encapsulation of doxorubicin inside liposomes or ferritin cages decreases cardiotoxicity while maintaining anticancer potency. We synthesized novel apoferritin- and liposome-encapsulated forms of doxorubicin ("Apodox" and "lip-8-dox") and compared its toxicity with doxorubicin and Myocet on prostate cell lines. Three different prostatic cell lines PNT1A, 22Rv1, and LNCaP were chosen. The toxicity of the modified doxorubicin forms was compared to conventional doxorubicin using the MTT assay, real-time cell impedance-based cell growth method (RTCA), and flow cytometry. The efficiency of doxorubicin entrapment was 56% in apoferritin cages and 42% in the liposome carrier. The accuracy of the RTCA system was verified by flow-cytometric analysis of cell viability. The doxorubicin half maximal inhibition concentrations (IC50) were determined as 170.5, 234.0, and 169.0 nM for PNT1A, 22Rv1, and LNCaP, respectively by RTCA. Lip8-dox is less toxic on the non-tumor cell line PNT1A compared to doxorubicin, while still maintaining the toxicity to tumorous cell lines similar to doxorubicin or epirubicin (IC50 = 2076.7 nM for PNT1A vs. 935.3 and 729.0 nM for 22Rv1 and LNCaP). Apodox IC50 was determined as follows: 603.1, 1344.2, and 931.2 nM for PNT1A, 22Rv1, and LNCaP.
阿霉素是一种有效的化疗药物，然而，其毒性是治疗中的一个重大限制。将阿霉素包裹在脂质体或铁蛋白笼内可降低心脏毒性，同时保持抗癌效力。我们合成了新型阿霉素的脱铁铁蛋白和脂质体包裹形式（“Apodox”和“lip-8-dox”），并将其与阿霉素和Myocet对前列腺细胞系的毒性进行了比较。选择了三种不同的前列腺细胞系PNT1A、22Rv1和LNCaP。使用MTT法、基于实时细胞阻抗的细胞生长方法（RTCA）和流式细胞术，将修饰后的阿霉素形式的毒性与传统阿霉素进行了比较。阿霉素在脱铁铁蛋白笼中的包封效率为56%，在脂质体载体中的包封效率为42%。通过流式细胞术分析细胞活力验证了RTCA系统的准确性。通过RTCA测定，阿霉素对PNT1A、22Rv1和LNCaP的半数最大抑制浓度（IC50）分别为170.5、234.0和169.0 nM。与阿霉素相比，Lip8-dox对非肿瘤细胞系PNT1A的毒性较小，同时仍保持对肿瘤细胞系的毒性，类似于阿霉素或表柔比星（PNT1A的IC50 = 2076.7 nM，而22Rv1和LNCaP的IC50分别为935.3和729.0 nM）。Apodox的IC50测定如下：PNT1A为603.1 nM、22Rv1为1344.2 nM和LNCaP为931.2 nM。
