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首页> 外文期刊>Process Biochemistry >The biological performance of purified supercoiled p53 plasmid DNA in different cancer cell lines
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The biological performance of purified supercoiled p53 plasmid DNA in different cancer cell lines

机译：纯化的超螺旋p53质粒DNA在不同癌细胞系中的生物学性能

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Tumor suppressor p53 remains one of the most interesting therapeutic targets in cancer gene therapy due to its consistent mutation in numerous cancers. Thus, the reinstatement of the p53 expression and function can be seen as an effective alternative for cancer treatment, motivating research in this field. In this study, L-methionine matrix was used to purify the supercoiled topoisoform of a plasmid DNA encoding the p53 protein. This pure biopharmaceutical was conjugated with liposomes to comprehensively analyze its in vitro performance and therapeutic potential in different cancer cell lines, including the lung and cervix models. A different profile of cellular responses was attained after the transfection of these cancer cell lines with the p53-pDNA. Actually, the in vitro transfection with pure sc p53-pDNA resulted in a higher expression of the tumor suppressor protein in cancer cells when compared with the native pDNA samples (oc + sc topoisoforms). Also, wild-type p53 expression following transfection was significantly higher in HeLa cervix cancer cells compared to that obtained in A549 lung cancer cells. Overall, our findings emphasize the potential of sc pDNA gene-based therapy, also raising awareness of the need to adjust the therapeutics, considering the feature of high heterogeneity of cancer cells.
机译：抑癌基因p53由于在许多癌症中具有一致的突变性，因此仍然是癌症基因治疗中最有趣的治疗靶标之一。因此，p53表达和功能的恢复可以看作是癌症治疗的有效替代方法，从而激发了该领域的研究。在这项研究中，L-蛋氨酸基质用于纯化编码p53蛋白的质粒DNA的超螺旋拓扑异构体。将该纯生物药物与脂质体偶联，以全面分析其在不同癌细胞系（包括肺和宫颈模型）中的体外性能和治疗潜力。用p53-pDNA转染这些癌细胞系后，获得了不同的细胞反应。实际上，与天然pDNA样品（oc + sc拓扑异构体）相比，纯sc p53-pDNA的体外转染导致癌细胞中肿瘤抑制蛋白的表达更高。另外，转染后的野生型p53表达在HeLa宫颈癌细胞中比在A549肺癌细胞中明显更高。总体而言，我们的发现强调了基于sc pDNA基因的治疗方法的潜力，同时考虑到癌细胞高度异质性的特征，也提高了人们对调整治疗方法的认识。

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