Ibrahim Bashiru, Akere Taiwo Hassan, Chakraborty Swaroop, Valsami-Jones Eugenia, Ali-Boucetta Hanene
Nanomedicine, Drug Delivery & Nanotoxicology (NDDN) Lab, School of Pharmacy, College of Medical and Dental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
School of Geography, Earth and Environmental Sciences, College of Life and Environmental Sciences, University of Birmingham, Birmingham B15 2TT, UK.
Pharmaceutics. 2024 Mar 11;16(3):380. doi: 10.3390/pharmaceutics16030380.
Heat-shock proteins (HSPs) are stress-responsive molecules belonging to the family of evolutionary molecular chaperones known to be crucial in many cancer types, including human alveolar adenocarcinoma cells (A549). These proteins are highly overexpressed in cancers to support their ability to accommodate imbalances in cell signalling, DNA alterations, proteins, and energy metabolism associated with oncogenesis. The current study evaluated the effects of gold nanoparticles (AuNPs) combined with cisplatin (CDDP) on molecular chaperone HSPs in A549 cells. It was found that AuNPs:CDDP decreased the percentage of cell viability (38.5%) measured using the modified lactated dehydrogenase (mLDH) and 3-[4,5-dimethylthiazole-2-yl]-2,5-diphenyltetrazolium bromide (MTT) assays. AuNPs:CDDP exposure caused a significant ( < 0.05) increase in reactive oxygen species (ROS) generation by 1.81-fold, apoptosis induction, and a decrease in the mitochondrial membrane potential (MMP) compared to AuNPs or CDDP alone. Similarly, exposure to the AuNPs:CDDP combination had pronounced cytotoxic effects on the expression of HSPs and PI3K/AKT/mTOR, as well as apoptosis-related proteins. The results demonstrate that the combination of AuNPs with CDDP might enhance the anticancer efficacy of CDDP.
热休克蛋白(HSPs)是应激反应分子,属于进化分子伴侣家族,已知在包括人肺泡腺癌细胞(A549)在内的许多癌症类型中起关键作用。这些蛋白质在癌症中高度过表达,以支持其适应与肿瘤发生相关的细胞信号传导失衡、DNA改变、蛋白质和能量代谢的能力。本研究评估了金纳米颗粒(AuNPs)与顺铂(CDDP)联合使用对A549细胞中分子伴侣HSPs的影响。研究发现,AuNPs:CDDP降低了使用改良乳酸脱氢酶(mLDH)和3-[4,5-二甲基噻唑-2-基]-2,5-二苯基四氮唑溴盐(MTT)测定法测得的细胞活力百分比(38.5%)。与单独使用AuNPs或CDDP相比,AuNPs:CDDP暴露导致活性氧(ROS)生成显著增加(<0.05)1.81倍,诱导凋亡,并降低线粒体膜电位(MMP)。同样,暴露于AuNPs:CDDP组合对HSPs和PI3K/AKT/mTOR以及凋亡相关蛋白的表达具有明显的细胞毒性作用。结果表明,AuNPs与CDDP联合使用可能会增强CDDP的抗癌疗效。