Cytotoxicity of dextran-graft-polyacrylamide/zinc oxide nanoparticles against doxorubicin-resistant breast cancer cells

P. Virych, V. Chumachenko, V. Pavlenko, N. Kutsevol
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Abstract

The toxicity of drugs for chemotherapy and cell resistance to their action are the main obstacles in anticancer therapy. Advances in nanotechnology may offer an alternative to traditional methods of anticancer therapy and overcoming drug resistance. The study was carried out on doxorubicin-resistant MCF-7/Dox breast cancer cells and BALB/3T3 clone A31 as a model of normal fibroblasts with the use of Dextran-graft-polyacrylamide/zinc oxide (D-PAA/ZnO) nanoparticles. Cytomorphological analysis was carried out after cells staining with acridine orange. Immunocytochemical study of Ki-67, p53, Bcl-2, Bax, E-cadherin, N-cadherin, СD44 expression was done. Cytotoxicity of D-PAA/ZnO nanoparticles (EC50 = 2.2 mM) against MCF-7/Dox cancer cells but not against normal fibroblasts was demonstrated. The increased expression of proapoptotic proteins, E-cadherin, CD44 and decreased expression of proliferation-associated marker Ki-67 in cancer cells treated with D-PAA/ZnO was revealed. Cytotoxicity of D-PAA/ZnO NPs against MCF-7/Dox cancer cells can be potentially used for elaboration of new approaches to cancer treatment. Keywords: breast cancer cells, cytotoxicity, dextran-graft-polyacrylamide, doxorubicin-resistance, fibroblasts, zinc oxide nanoparticles
葡聚糖接枝聚丙烯酰胺/氧化锌纳米粒子对多柔比星耐药乳腺癌细胞的细胞毒性
化疗药物的毒性和细胞对其作用的抗药性是抗癌治疗的主要障碍。纳米技术的进步可能为传统的抗癌疗法和克服耐药性提供了一种替代方法。本研究使用葡聚糖接枝聚丙烯酰胺/氧化锌(D-PAA/ZnO)纳米粒子对多柔比星耐药的 MCF-7/Dox 乳腺癌细胞和作为正常成纤维细胞模型的 BALB/3T3 克隆 A31 进行了研究。细胞经吖啶橙染色后进行了细胞形态学分析。对 Ki-67、p53、Bcl-2、Bax、E-cadherin、N-cadherin 和 СD44 的表达进行了免疫细胞化学研究。结果表明,D-PAA/氧化锌纳米粒子(EC50 = 2.2 mM)对 MCF-7/Dox 癌细胞具有细胞毒性,但对正常成纤维细胞没有毒性。经 D-PAA/ZnO 处理的癌细胞中,促凋亡蛋白、E-cadherin、CD44 的表达增加,增殖相关标志物 Ki-67 的表达减少。D-PAA/ZnO NPs对MCF-7/Dox癌细胞的细胞毒性可用于开发治疗癌症的新方法。关键词:乳腺癌细胞、细胞毒性、葡聚糖接枝聚丙烯酰胺、多柔比星抗性、成纤维细胞、氧化锌纳米颗粒
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