Alaa Hadi-Al-Ward Noorulhuda, Ebrahimi Mehdi, Zare Karizi Shohre
Department of Genetics, Faculty of Converging Sciences and Technologies, Science and Research Branch, Islamic Azad University, Tehran, Iran.
Department of Biochemistry and Biophysics, College of Biological Sciences, Varamin-Pishva branch, Islamic Azad University, Pishva, Iran.
Iran J Pharm Res. 2024 May 29;23(1):e144287. doi: 10.5812/ijpr-144287. eCollection 2024 Jan-Dec.
The incidence of colorectal cancer is increasing globally. Daunorubicin (DNR), an anthracycline antibiotic, is effective against various cancers. The PI3K/AKT/mTOR signaling pathway is crucial in regulating cell growth and cancer growth.
This study aims to evaluate the effects of liposomal daunorubicin (Lip-DNR) on cell proliferation and cell death induction in HCT116 cells compared to free daunorubicin.
Lip-DNR was synthesized, and its shape and size were analyzed using FE-SEM imaging. HCT116 cells were treated with Lip-DNR concentrations of 0 (control), 0.125, 0.25, 0.5, 1, and 2 μm for 48 hours to determine the IC50. The effects of free (0.5 μm) and liposomal DNR (IC50 of 0.43 μm) on PI3K mRNA levels were assessed using real-time PCR. The cell cycle was analyzed by flow cytometry.
FE-SEM imaging showed that the liposomes are spherical and range from 50 - 100 nm in size. Lip-DNR induced cell death in HCT116 cells in a dose-dependent manner, with 0.5 μm Lip-DNR causing more cell death than an equivalent concentration of free DNR. Analysis of PI3K gene expression showed that DNR decreases PI3K gene transcription in HCT116 cells, with Lip-DNR having a more substantial effect than the free form. Both forms reduced the proportion of G2/M phase cells, but Lip-DNR was more effective at inhibiting cell proliferation in HCT116 cells.
DNR inhibits the proliferation of HCT116 cells by downregulating PI3K gene expression and enhancing cell death, with the liposomal form demonstrating stronger effects than the free form.
全球范围内，结直肠癌的发病率正在上升。柔红霉素（DNR）是一种蒽环类抗生素，对多种癌症有效。PI3K/AKT/mTOR信号通路在调节细胞生长和癌症生长中起关键作用。
本研究旨在评估脂质体柔红霉素（Lip-DNR）与游离柔红霉素相比，对HCT116细胞增殖和诱导细胞死亡的影响。
合成Lip-DNR，并使用场发射扫描电子显微镜（FE-SEM）成像分析其形状和大小。用浓度为0（对照）、0.125、0.25、0.5、1和2μm的Lip-DNR处理HCT116细胞48小时以确定半数抑制浓度（IC50）。使用实时聚合酶链反应（PCR）评估游离（0.5μm）和脂质体DNR（IC50为0.43μm）对PI3K信使核糖核酸（mRNA）水平的影响。通过流式细胞术分析细胞周期。
FE-SEM成像显示脂质体呈球形，大小在50 - 100纳米之间。Lip-DNR以剂量依赖的方式诱导HCT116细胞死亡，0.5μm的Lip-DNR比同等浓度的游离DNR导致更多细胞死亡。PI3K基因表达分析表明，DNR降低HCT116细胞中PI3K基因转录，Lip-DNR的作用比游离形式更显著。两种形式均降低了G2/M期细胞比例，但Lip-DNR在抑制HCT116细胞增殖方面更有效。
DNR通过下调PI3K基因表达和增强细胞死亡来抑制HCT116细胞增殖，脂质体形式的效果比游离形式更强。
