HepG2 cells (HCC), characterized by epithelial-like morphology, high proliferation rates, and nontumorigenicity, require cost-effective and efficient treatment. Silymarin, a flavonoid extract of Silybum marianum, is effective in the treatment of HCC. Here, we have reported a comparative anticancer study of the well-characterized nanoformulations of lactobionic acid-adorned porous PLGA-encapsulated silymarin (LA-PLGA-Sil) with only porous PLGA-encapsulated silymarin (PLGA-Sil) against HepG2 cells. Treatment of HepG2 cells with LA-PLGA-Sil produced a significant deterioration in cell viability at an essentially low dose as compared with PLGA-Sil, due to the adorned lactobionic acid moiety, which results in better targeting. p53, a tumor suppressor gene, essentially initiates apoptosis in cells procuring wild-type p53 (p53 +/+). In our report, treatment of HepG2 cells (p53 +/+) with LA-PLGA-Sil activated p53, which in turn inhibited the proliferation of cells by instigating cell-cycle arrest and apoptosis in a concentration-dependent manner and simultaneously stabilized the nuclear translocation of NFκB-p65. To explore the effect of LA-PLGA-Sil on the expression of microRNA, we observed that LA-PLGA-Sil markedly upregulated the miR-29b in human HCC cells. Reactivation of the p53 gene by miR-29b targeted Bcl-2 and triggered the sequential activation of mediators such as proapoptotic Bax protein, release of cytochrome c, and the activation of caspase proteins (caspase-3 and caspase-9). Furthermore, the overexpression of NFκB-p65 in HepG2 cells reversed the repression, and this stabilization effect of LA-PLGA-Sil on the nuclear translocation of p65 led to the significant downregulation of miR-29b and successively decreased the p53 expression in LA-PLGA-Sil-treated cells, thereby providing a survival mechanism to HepG2. In entirety, our study demonstrated the extensive potential of LA-PLGA-Sil to instigate the cell death of HepG2 cells via apoptosis by targeting the miR-29b/p53 axis through the stabilization of NFκB. It also impaired the migratory activity of HepG2 cells and thereby furnished a comprehensive way to HCC therapeutic treatment.

中文翻译：

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负载水飞蓟素的乳糖酸共轭多孔 PLGA 纳米颗粒诱导肝癌细胞凋亡

HepG2 细胞 (HCC) 具有上皮样形态、高增殖率和非致瘤性，需要经济高效的治疗。水飞蓟素，S的类黄酮提取物lybum marianum，对HCC的治疗有效。在这里，我们报道了对具有良好表征的乳糖酸修饰的多孔 PLGA 封装的水飞蓟素 (LA-PLGA-Sil) 的纳米制剂与仅多孔 PLGA 封装的水飞蓟素 (PLGA-Sil) 对抗 HepG2 细胞的比较抗癌研究。与 PLGA-Sil 相比，用 LA-PLGA-Sil 处理 HepG2 细胞会导致细胞活力显着下降，这是由于修饰的乳糖酸部分导致了更好的靶向性。p53 是一种肿瘤抑制基因，主要在获得野生型 p53 (p53 +/+) 的细胞中启动细胞凋亡。在我们的报告中，用 LA-PLGA-Sil 激活的 p53 处理 HepG2 细胞 (p53 +/+)，反过来，它通过以浓度依赖性方式引发细胞周期停滞和细胞凋亡来抑制细胞增殖，同时稳定 NFκB-p65 的核转位。为了探索 LA-PLGA-Sil 对 microRNA 表达的影响，我们观察到 LA-PLGA-Sil 显着上调人 HCC 细胞中的 miR-29b。miR-29b 重新激活 p53 基因靶向 Bcl-2 并触发介质的顺序激活，例如促凋亡 Bax 蛋白、细胞色素的释放c，以及 caspase 蛋白（caspase-3 和 caspase-9）的激活。此外，HepG2 细胞中 NFκB-p65 的过表达逆转了抑制，而 LA-PLGA-Sil 对 p65 核转位的这种稳定作用导致 miR-29b 的显着下调并相继降低了 LA-PLGA 中 p53 的表达-Sil 处理的细胞，从而为 HepG2 提供生存机制。总的来说，我们的研究证明了 LA-PLGA-Sil 通过稳定 NFκB 靶向 miR-29b/p53 轴，通过细胞凋亡引发 HepG2 细胞死亡的广泛潜力。它还损害了 HepG2 细胞的迁移活性，从而为 HCC 治疗提供了一种综合途径。