Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.
Department of Biology, Faculty of Basic Sciences, Shahrekord Branch, Islamic Azad University, Shahrekord, Iran.
Naunyn Schmiedebergs Arch Pharmacol. 2024 Nov;397(11):8771-8783. doi: 10.1007/s00210-024-03182-9. Epub 2024 Jun 5.
This study aimed to address the challenges of treating advanced stages of colon cancer (CRC) by exploring potential therapeutic options. The research focused on the genetic aspects of CRC, specifically the mutation rate of the KRAS gene, along with other genes like TTN, APC, MUC16, and TP53, using the TCGA dataset. Additionally, the study investigated the efficacy of Oleuropein, a polyphenolic compound found in olives, in combating CRC by using iron oxide nanoparticles coated with glucose and conjugated with Oleuropein. The study characterized the physicochemical properties of the nanoparticles, and the cytotoxic effects of the nanoparticles were evaluated on CRC and normal fibroblast cell lines, demonstrating significantly higher cytotoxicity against CRC cells compared to normal cells. Furthermore, the study analyzed gene expression changes using the GSE124627 dataset to understand the influence of KRAS alterations. It identified numerous upregulated and downregulated genes in KRAS-overexpressing samples, suggesting their involvement in critical cancer-related pathways. These findings suggest that KRAS-influenced genes could serve as potential therapeutic targets for CRC treatment. The study also examined the expression levels of identified genes in CRC samples compared to normal samples. Among the upregulated genes, 22 showed significant increases in cancer samples, while 14 downregulated genes exhibited decreased expression in both KRAS-influenced and cancer samples. Cox regression analysis identified specific upregulated genes, including ANKZF1, SNAI1, PPFIA4, SIX4, and NOTUM, associated with poor prognosis. Kaplan-Meier analysis further confirmed the correlation between increased expression of these genes and higher patient mortality rates. In conclusion, this study provided valuable insights into the genetic aspects of CRC and potential therapeutic strategies. The use of Oleuropein-conjugated iron oxide nanoparticles showed promising cytotoxic effects on colon cancer cells. These findings contribute to advancing our understanding of CRC and offer potential targets for further investigation and the development of novel therapeutic approaches.
本研究旨在通过探索潜在的治疗选择来解决晚期结肠癌（CRC）的治疗挑战。该研究专注于 CRC 的遗传方面，特别是 KRAS 基因的突变率，以及使用 TCGA 数据集的其他基因，如 TTN、APC、MUC16 和 TP53。此外，该研究还研究了橄榄叶中发现的多酚化合物橄榄苦苷，通过用葡萄糖涂覆的氧化铁纳米粒子并与橄榄苦苷结合，来对抗 CRC 的疗效。该研究对纳米粒子的物理化学性质进行了表征，并在 CRC 和正常成纤维细胞系上评估了纳米粒子的细胞毒性作用，结果表明，与正常细胞相比，纳米粒子对 CRC 细胞具有明显更高的细胞毒性。此外，该研究还使用 GSE124627 数据集分析了基因表达变化，以了解 KRAS 改变的影响。它确定了 KRAS 过表达样本中许多上调和下调的基因，表明它们参与了关键的癌症相关途径。这些发现表明，KRAS 影响的基因可能成为 CRC 治疗的潜在治疗靶点。该研究还检查了 CRC 样本与正常样本中鉴定的基因的表达水平。在上调的基因中，有 22 个在癌症样本中显著增加，而在受 KRAS 影响的样本和癌症样本中表达下调的有 14 个基因。Cox 回归分析确定了特定的上调基因，包括 ANKZF1、SNAI1、PPFIA4、SIX4 和 NOTUM，与预后不良相关。Kaplan-Meier 分析进一步证实了这些基因表达增加与患者死亡率升高之间的相关性。总之，本研究为 CRC 的遗传方面和潜在的治疗策略提供了有价值的见解。用橄榄苦苷结合的氧化铁纳米粒子对结肠癌细胞表现出有希望的细胞毒性作用。这些发现有助于我们深入了解 CRC，并为进一步研究和开发新的治疗方法提供了潜在的目标。
