Investigation of the Cytotoxic and Antiproliferative Effects of Liposomal Daunorubicin on Human Colorectal Cancer (HCT116) Cell Line.

IF 1.8 4区医学 Q3 PHARMACOLOGY & PHARMACY Iranian Journal of Pharmaceutical Research Pub Date : 2024-05-29 eCollection Date: 2024-01-01 DOI:10.5812/ijpr-144287

Noorulhuda Alaa Hadi-Al-Ward, Mehdi Ebrahimi, Shohre Zare Karizi

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Abstract

Background: 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.

Objectives: 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.

Methods: 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.

Results: 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.

Conclusions: 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.

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柔红霉素脂质体对人大肠癌（HCT116）细胞株的细胞毒和抗增殖作用的研究。

背景：结直肠癌的发病率在全球范围内呈上升趋势。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肿瘤生长中起重要作用。目的：本研究旨在评价脂质体柔红霉素（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。方法：合成Lip-DNR，利用FE-SEM对其形状和大小进行分析。用浓度为0（对照）、0.125、0.25、0.5、1和2 μm的Lip-DNR处理HCT116细胞48小时，测定IC50。实时荧光定量PCR检测游离DNR （0.5 μm）和脂质体DNR （IC50为0.43 μm）对PI3K mRNA水平的影响。流式细胞术分析细胞周期。结果：FE-SEM成像显示脂质体为球形，大小在50 ~ 100 nm之间。Lip-DNR诱导HCT116细胞死亡呈剂量依赖性，0.5 μm Lip-DNR比同等浓度的游离DNR导致更多细胞死亡。PI3K基因表达分析显示，DNR降低了HCT116细胞中PI3K基因的转录，且Lip-DNR的作用比游离形式更为显著。两种形式均降低了G2/M期细胞的比例，但Lip-DNR对HCT116细胞增殖的抑制作用更有效。结论：DNR通过下调PI3K基因表达，促进细胞死亡来抑制HCT116细胞的增殖，且脂质体形式的作用强于游离形式。

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来源期刊

Iranian Journal of Pharmaceutical Research 医学-药学

CiteScore

3.40

自引率

6.20%

发文量

审稿时长

2 months

期刊介绍： The Iranian Journal of Pharmaceutical Research (IJPR) is a peer-reviewed multi-disciplinary pharmaceutical publication, scheduled to appear quarterly and serve as a means for scientific information exchange in the international pharmaceutical forum. Specific scientific topics of interest to the journal include, but are not limited to: pharmaceutics, industrial pharmacy, pharmacognosy, toxicology, medicinal chemistry, novel analytical methods for drug characterization, computational and modeling approaches to drug design, bio-medical experience, clinical investigation, rational drug prescribing, pharmacoeconomics, biotechnology, nanotechnology, biopharmaceutics and physical pharmacy.