Zhang Xi-Feng, Yan Qi, Shen Wei, Gurunathan Sangiliyandi
College of Biological and Pharmaceutical Engineering, Wuhan Polytechnic University, Wuhan 430023, China.
Key Laboratory of Animal Reproduction and Germplasm Enhancement in Universities of Shandong, College of Animal Science and Technology, Qingdao Agricultural University, Qingdao 266109, China.
Int J Mol Sci. 2016 Aug 19;17(8):1354. doi: 10.3390/ijms17081354.
Cervical cancer ranks seventh overall among all types of cancer in women. Although several treatments, including radiation, surgery and chemotherapy, are available to eradicate or reduce the size of cancer, many cancers eventually relapse. Thus, it is essential to identify possible alternative therapeutic approaches for cancer. We sought to identify alternative and effective therapeutic approaches, by first synthesizing palladium nanoparticles (PdNPs), using a novel biomolecule called saponin. The synthesized PdNPs were characterized by several analytical techniques. They were significantly spherical in shape, with an average size of 5 nm. Recently, PdNPs gained much interest in various therapies of cancer cells. Similarly, histone deacetylase inhibitors are known to play a vital role in anti-proliferative activity, gene expression, cell cycle arrest, differentiation and apoptosis in various cancer cells. Therefore, we selected trichostatin A (TSA) and PdNPs and studied their combined effect on apoptosis in cervical cancer cells. Cells treated with either TSA or PdNPs showed a dose-dependent effect on cell viability. The combinatorial effect, tested with 50 nM TSA and 50 nMPdNPs, had a more dramatic inhibitory effect on cell viability, than either TSA or PdNPs alone. The combination of TSA and PdNPs had a more pronounced effect on cytotoxicity, oxidative stress, mitochondrial membrane potential (MMP), caspase-3/9 activity and expression of pro- and anti-apoptotic genes. Our data show a strong synergistic interaction between TSA and PdNPs in cervical cancer cells. The combinatorial treatment increased the therapeutic potential and demonstrated relevant targeted therapy for cervical cancer. Furthermore, we provide the first evidence for the combinatory effect and cytotoxicity mechanism of TSA and PdNPs in cervical cancer cells.
宫颈癌在女性所有类型癌症中总体排名第七。尽管有多种治疗方法,包括放疗、手术和化疗,可用于根除癌症或缩小肿瘤大小,但许多癌症最终还是会复发。因此,确定可能的癌症替代治疗方法至关重要。我们试图通过首先使用一种名为皂苷的新型生物分子合成钯纳米颗粒(PdNPs)来确定替代且有效的治疗方法。通过多种分析技术对合成的PdNPs进行了表征。它们形状显著呈球形,平均尺寸为5纳米。最近,PdNPs在癌细胞的各种治疗中引起了广泛关注。同样,组蛋白去乙酰化酶抑制剂在各种癌细胞的抗增殖活性、基因表达、细胞周期停滞、分化和凋亡中起着至关重要的作用。因此,我们选择了曲古抑菌素A(TSA)和PdNPs,并研究了它们对宫颈癌细胞凋亡的联合作用。用TSA或PdNPs处理的细胞对细胞活力呈现剂量依赖性影响。用50 nM TSA和50 nM PdNPs测试的联合作用对细胞活力的抑制作用比单独使用TSA或PdNPs更为显著。TSA和PdNPs的联合对细胞毒性、氧化应激、线粒体膜电位(MMP)、半胱天冬酶-3/9活性以及促凋亡和抗凋亡基因的表达有更明显的影响。我们的数据显示TSA和PdNPs在宫颈癌细胞中存在强烈的协同相互作用。联合治疗提高了治疗潜力,并证明了对宫颈癌的相关靶向治疗。此外,我们首次提供了TSA和PdNPs在宫颈癌细胞中的联合作用和细胞毒性机制的证据。