Effect of Iron Superoxide and Nickel Oxide Nanoparticles Alone and Combined with Coenzyme Q10 on hsa_circ_0001518 Expression in Breast Tumor-bearing BALB/c Mice

Ghazaleh Ganjipour, M. Heshmati, M. Hashemi, M. Entezari
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Abstract

Background: Breast cancer is considered the second prevailed type of cancer among women. Circular RNAs are a group of non-coding RNAs that play a significant role in tumorigenesis and the progression of malignancies. This study aimed to determine the inhibitory concentration (IC50) of iron superoxide (Fe2O3) and nickel oxide (NiO) nanoparticles and coenzyme Q10 (Q10) antioxidant against 4T1 cell line and their single and combination treatment effect on hsa_circ_0001518 expression in healthy and breast tumor mice. Methods: The 4T1 cell line was cultivated and treated with Fe2O3 (50, 100, 150, and 200 μg/mL) and NiO (10, 20, 30, and 40 μg/mL) nanoparticles, and Q10 antioxidant (20, 60, 80, and 100 μg/mL) for 48 hours. Cell viability was measured using the MTT assay. The expression of hsa_circ_0001518 after treatment with the half-maximal inhibitory concentration (IC50) of all single and combined antioxidant and NPs in healthy and breast tumor-bearing mice were evaluated by qRT-PCR. Results: The IC50 of Fe2O3 and NiO nanoparticles and Q10 antioxidant after 48h was 92.42 μg/mL, 21.49 μg/mL, and 83.47 μg/mL, respectively. The qRT-PCR results showed that combined treatment with antioxidant and NPs caused a more significant downregulation in the expression of has_circ1518 in breast tumor-bearing mice than either agent alone. In addition, combined treatment with antioxidant and NPs caused a more significant downregulation in the expression of has_circ1518 in breast tumor-bearing mice than either agent alone. Conclusion: This study suggests that the combined treatment of Fe2O3 and NiO nanoparticles with Q10 could be exploited as a potential source for developing novel drugs against breast cancer.
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超氧化铁和氧化镍纳米颗粒单独及联合辅酶Q10对乳腺荷瘤BALB/c小鼠hsa_circ_0001518表达的影响
背景:乳腺癌被认为是女性中第二常见的癌症类型。环状rna是一组在肿瘤发生和恶性肿瘤进展中起重要作用的非编码rna。本研究旨在测定超氧化铁(Fe2O3)、氧化镍(NiO)纳米颗粒和辅酶Q10 (Q10)抗氧化剂对4T1细胞系的抑制浓度(IC50)及其单独和联合对健康和乳腺肿瘤小鼠hsa_circ_0001518表达的影响。方法:用Fe2O3(50、100、150、200 μg/mL)、NiO(10、20、30、40 μg/mL)纳米颗粒和Q10抗氧化剂(20、60、80、100 μg/mL)分别培养4T1细胞系48 h。采用MTT法测定细胞活力。采用qRT-PCR方法检测健康小鼠和乳腺荷瘤小鼠中hsa_circ_0001518蛋白的表达情况。结果:Fe2O3、NiO纳米颗粒和Q10抗氧化剂48h后的IC50分别为92.42 μg/mL、21.49 μg/mL和83.47 μg/mL。qRT-PCR结果显示,抗氧化剂和NPs联合治疗对乳腺荷瘤小鼠has_circ1518表达的下调作用比单独用药更显著。此外,与抗氧化剂和NPs联合处理比单独使用任何一种药物更显著地下调了乳腺荷瘤小鼠has_circ1518的表达。结论:该研究表明,Q10联合处理Fe2O3和NiO纳米颗粒可作为开发抗乳腺癌新药的潜在来源。
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