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比较与拉帕替尼偶联的氧化铜纳米粒子对乳腺癌(MDA-MB-231)和肺癌(A549)细胞系的毒性作用。

Comparing the toxicity effects of copper oxide nanoparticles conjugated with Lapatinib on breast (MDA-MB-231) and lung (A549) cancer cell lines.

机构信息

Department of Biology, Rasht Branch, Islamic Azad University, Rasht, Iran.

Department of Biology, Faculty of Science, Arak University, Arak, 384817758, Iran.

出版信息

Naunyn Schmiedebergs Arch Pharmacol. 2024 Sep;397(9):6855-6866. doi: 10.1007/s00210-024-03071-1. Epub 2024 Apr 2.

Abstract

In recent years, the increase in cancer morbidity and mortality has presented scientists with a major challenge in developing new therapeutic agents against cancer cells. This study aims to characterize the anticancer effects of copper oxide nanoparticles (NPs) conjugated with Lapatinib (CuO@Lapatinib) on breast and lung cancer cell lines. The physicochemical properties of the NPs were characterized by fourier-transform infrared (FT-IR) spectroscopy, X-ray diffraction (XRD), scanning and transmission electron microscopy, energy dispersive X-ray spectroscopy (EDS), dynamic light scattering (DLS), and zeta potential analyses. The antiproliferative potential of the NPs in the breast (MDA-MB-231) and lung (A549) cancer cell lines and a normal cell line (MRC5) was investigated by MTT (3-(4,5-Dimethylthiazol-2-yl)-2,5-Diphenyltetrazolium Bromide) assay. Flow cytometry and Hoechst staining were used to evaluate cell apoptosis and cell cycle analysis. The reactive oxygen species (ROS) levels in the treated and control cells were also determined. The NPs were spherical, with a size range of 20-59nm, a DLS size of 338nm, and a zeta potential of -42.9 mV. The half maximal inhibitory concentration (IC) of CuO@Lapatinib NPs for the normal, breast cancer, and lung cancer cell lines was 105, 98, and 87 µg/ml, respectively. Treatment with CuO@Lapatinib NPs caused considerable apoptosis induction in breast cancer (from 0.65% to 68.96%) and lung cancer cell lines (from 1.11% to 44.11%). Also, an increased level of cell cycle arrest at the S phase was observed in both cancer cell lines. The ROS level in the breast and lung cancer cell lines after treatment with CuO@Lapatinib NPs increased by 3.45 and 21.04 folds, respectively. Nuclear morphological alterations, including chromatin condensation and fragmentation, were observed in both cancer cell lines. This study indicates CuO@Lapatinib is a potent antiproliferative compound with more efficient inhibitory effects on lung cancer than breast cancer cells, which can be related to the higher ROS generation in the A549 cell line.

摘要

近年来,癌症发病率和死亡率的增加给科学家们带来了一个重大挑战,即开发针对癌细胞的新治疗药物。本研究旨在研究氧化铜纳米粒子(NPs)与拉帕替尼(CuO@Lapatinib)缀合对乳腺癌和肺癌细胞系的抗癌作用。通过傅里叶变换红外(FT-IR)光谱、X 射线衍射(XRD)、扫描和透射电子显微镜、能量色散 X 射线光谱(EDS)、动态光散射(DLS)和 Zeta 电位分析对 NPs 的物理化学性质进行了表征。通过 MTT(3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四唑溴盐)测定法研究了 NPs 在乳腺癌(MDA-MB-231)和肺癌(A549)细胞系和正常细胞系(MRC5)中的增殖潜力。流式细胞术和 Hoechst 染色用于评估细胞凋亡和细胞周期分析。还测定了处理和对照细胞中活性氧(ROS)的水平。NPs 呈球形,尺寸范围为 20-59nm,DLS 尺寸为 338nm,Zeta 电位为-42.9mV。CuO@Lapatinib NPs 对正常、乳腺癌和肺癌细胞系的半最大抑制浓度(IC)分别为 105、98 和 87μg/ml。CuO@Lapatinib NPs 处理导致乳腺癌(从 0.65%到 68.96%)和肺癌细胞系(从 1.11%到 44.11%)的凋亡诱导相当大。还观察到两种癌细胞系的细胞周期停滞在 S 期的水平增加。用 CuO@Lapatinib NPs 处理后,乳腺癌和肺癌细胞系中的 ROS 水平分别增加了 3.45 倍和 21.04 倍。在两种癌细胞系中都观察到核形态改变,包括染色质浓缩和片段化。本研究表明,CuO@Lapatinib 是一种有效的增殖抑制剂,对肺癌细胞的抑制作用比对乳腺癌细胞更有效,这可能与 A549 细胞系中产生更高的 ROS 有关。

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