Interdisciplinary Research Development Center, Iran University of Medical Sciences, Tehran, Iran; Department of Biochemistry, School of Medicine, Iran University of Medical Sciences, Tehran, Iran.
Department of Medical Nanotechnology, Faculty of Advanced Medical Science, Medical University of Tabriz, Tabriz, Iran; Drug Applied Research Center, Tabriz University of Medical Sciences, Tabriz, Iran.
Pathol Res Pract. 2024 Nov;263:155667. doi: 10.1016/j.prp.2024.155667. Epub 2024 Oct 22.
Ovarian cancer is one of the most common malignancy in women with significant mortality rate due to the resistance to chemotherapy drugs. Doxorubicin (DOX) is a chemotropic agent in ovarian cancer treatment. Overexpression of multidrug resistance (MDR) genes, such as ABCB1, in cancer cells after chemotherapy is one of main problems in clinical applications. Here we have compared the efficiency of doxorubicin-loaded (NIPAAM-DMAEMA) FeO nanocomposite (DOX-NANO) against DOX on ABCB1(MDR1) gene expression in the ovarian cancer cell line.
The cell viability of SKOV-3 cells were evaluated by MTT assay. Real Time PCR was used to measure the expression level of MDR1. MTT data were normalized in 10 different attribute weighting models, also to reveal the interaction between DOX, ABCB1, and ovarian cancer genes, Pathway Studio Database (Elsevier) was used.
Cell viability of SKOV-3cells was significantly decreased after 24, 48 and 72 hours (P < 0.0001) of either DOX with IC50 22.38, 0.61 and 0.072 µg/ml or DOX-NANO treatment with IC50 11.54, 1.01, 0.0126 µg/ ml respectively.
Notable decrease in the expression of MDR gene, ABCB1, was observed 48 hours after treatment with DOX-NANO (P < 0.0001) with 26 % in the assessed with control group. Meta-analysis showed the concentration of 10 μg/ml variables was the second most significant feature, whereas the concentration of 0.01 μg/ml recognized the lowest weights. Also, LGALS3 is an extra cellular receptor with upregulation in ovarian cancer that interacts with ABCB1.
Our findings highlight the beneficial effects of DOX delivery in ovarian cancer cells by nanocomposite as efficient drug delivery method. DOX-NANO is a promising therapeutic reagent to overcome chemotherapy resistance in ovarian cancer.
卵巢癌是女性最常见的恶性肿瘤之一，由于对化疗药物的耐药性，死亡率很高。阿霉素（DOX）是卵巢癌治疗中的一种化疗药物。化疗后癌细胞中多药耐药（MDR）基因的过度表达，如 ABCB1，是临床应用中的主要问题之一。在这里，我们比较了载阿霉素（NIPAAM-DMAEMA）FeO 纳米复合材料（DOX-NANO）与 DOX 对卵巢癌细胞系 ABCB1（MDR1）基因表达的疗效。
用 MTT 法评价 SKOV-3 细胞的细胞活力。实时 PCR 用于测量 MDR1 的表达水平。将 MTT 数据归一化为 10 种不同属性加权模型，还使用了 Pathway Studio 数据库（Elsevier）来揭示 DOX、ABCB1 和卵巢癌基因之间的相互作用。
用 DOX 处理 SKOV-3 细胞 24、48 和 72 小时后，细胞活力明显下降（P <0.0001），IC50 分别为 22.38、0.61 和 0.072μg/ml，或用 DOX-NANO 处理 11.54、1.01 和 0.0126μg/ml。
用 DOX-NANO 处理后 48 小时，MDR 基因 ABCB1 的表达明显下降（P <0.0001），与对照组相比下降了 26%。Meta 分析显示，浓度为 10μg/ml 的变量是第二大显著特征，而浓度为 0.01μg/ml 的变量识别出的权重最低。此外，LGALS3 是一种细胞外受体，在卵巢癌中上调，并与 ABCB1 相互作用。
我们的研究结果强调了纳米复合材料在卵巢癌细胞中递送 DOX 的有益效果，这是一种有效的药物递送方法。DOX-NANO 是克服卵巢癌化疗耐药性的有前途的治疗试剂。
