基因增强疗法需要替换癌细胞中异常的抑癌基因。在这项研究中,我们对 BRCA1/2 肿瘤抑制基因进行了基因增强,以延缓乳腺癌小鼠模型中的肿瘤发展。我们配制了无机碳酸盐磷灰石 (CA) 纳米颗粒 (NP),用于在体外和体内携带和递送纯化的携带 BRCA1/2 基因的质粒 DNA。通过 MTT 测定评估了 BRCA1/2 质粒负载 NPs 递送对三种乳腺癌细胞系(如 MCF-7、MDA-MB-231 和 4T1)细胞活力的影响。MCF-7 细胞系的结果显示,与对照组相比,用 CA NPs 转染 BRCA 1/2 质粒显着减少了癌细胞的生长。此外,我们注意到 4T1 鼠癌细胞系中可能存在细胞毒性模式。在用载有 BRCA1 质粒的 NP 转染和蛋白质印迹分析后,检测到 MAPK 信号通路的磷酸化 MAPK 蛋白显着减少,表明生长信号减少。此外,在 4T1 诱导的乳腺癌小鼠模型中进行的体内研究表明,在接受 BRCA1 + NPs 和 BRCA2 + NPs 制剂静脉内治疗的小鼠组中,肿瘤生长速率和最终体积显着降低。我们的结果表明,将 BRCA1/2 质粒掺入 CA NPs 可以减轻乳腺肿瘤的生长,表明它们在乳腺癌治疗中的应用。在 4T1 诱导的乳腺癌小鼠模型中进行的体内研究表明,在用 BRCA1 + NPs 和 BRCA2 + NPs 制剂静脉内治疗的小鼠组中,肿瘤生长速率和最终体积显着降低。我们的结果表明,将 BRCA1/2 质粒掺入 CA NPs 可以减轻乳腺肿瘤的生长,表明它们在乳腺癌治疗中的应用。在 4T1 诱导的乳腺癌小鼠模型中进行的体内研究表明,在用 BRCA1 + NPs 和 BRCA2 + NPs 制剂静脉内治疗的小鼠组中,肿瘤生长速率和最终体积显着降低。我们的结果表明,将 BRCA1/2 质粒掺入 CA NPs 可以减轻乳腺肿瘤的生长,表明它们在乳腺癌治疗中的应用。
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Retarding breast tumor growth with nanoparticle-facilitated intravenous delivery of BRCA1 and BRCA2 tumor suppressor genes
Gene augmentation therapy entails replacement of the abnormal tumor suppressor genes in cancer cells. In this study, we performed gene augmentation for BRCA1/2 tumor suppressors in order to retard tumor development in breast cancer mouse model. We formulated inorganic carbonate apatite (CA) nanoparticles (NPs) to carry and deliver the purified BRCA1/2 gene- bearing plasmid DNA both in vitro and in vivo. The outcome of BRCA1/2 plasmid-loaded NPs delivery on cellular viability of three breast cancer cell lines such as MCF-7, MDA-MB-231 and 4T1 were evaluated by MTT assay. The result in MCF-7 cell line exhibited that transfection of BRCA 1/2 plasmids with CA NPs significantly reduced cancer cell growth in comparison to control group. Moreover, we noticed a likely pattern of cellular cytotoxicity in 4T1 murine cancer cell line. Following transfection with BRCA1 plasmid-loaded NPs, and Western blot analysis, a notable reduction in the phospho-MAPK protein of MAPK signaling pathway was detected, revealing reduced growth signal. Furthermore, in vivo study in 4T1 induced breast cancer mouse model showed that the tumor growth rate and final volume were decreased significantly in the mouse group treated intravenously with BRCA1 + NPs and BRCA2 + NPs formulations. Our results established that BRCA1/2 plasmids incorporated into CA NPs mitigated breast tumor growth, signifying their application in the therapy for breast cancer.