Yuan Yu-Guo, Gurunathan Sangiliyandi
College of Veterinary Medicine/Animal Science and Technology/Jiangsu Co-Innovation Center for Prevention and Control of Important Animal Infectious Diseases and Zoonosis, Yangzhou University, Yangzhou, Jiangsu, China.
Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases, Yangzhou University, Yangzhou, China.
Int J Nanomedicine. 2017 Sep 5;12:6537-6558. doi: 10.2147/IJN.S125281. eCollection 2017.
Cisplatin (Cis) is a widely used chemotherapeutic drug for treating a variety of cancers, due to its ability to induce cell death in cancer cells significantly. Recently, graphene and its modified nanocomposites have gained much interest in cancer therapy, due to their unique physicochemical properties. The objective of this study was to investigate the combination effect of Cis and a reduced graphene oxide-silver nanoparticle nanocomposite (rGO-AgNPs) in human cervical cancer (HeLa) cells.
We synthesized AgNPs, rGO, and rGO-AgNP nanocomposites using C-phycocyanin. The synthesized nanomaterials were characterized using various analytical techniques. The anticancer properties of the Cis, rGO-AgNPs, and combination of Cis and rGO-AgNPs were evaluated using a series of cellular assays, such as cell viability, cell proliferation, LDH leakage, reactive oxygen species generation, and cellular levels of oxidative and antioxidative stress markers such as malondialdehyde, glutathione, SOD, and CAT. The expression of proapoptotic, antiapoptotic, and autophagy genes were measured using real-time reverse-transcription polymerase chain reaction.
The synthesized AgNPs were well dispersed, homogeneous, and spherical, with an average size of 10 nm and uniformly distributed on graphene sheets. Cis, GO, rGO, AgNPs, and rGO-AgNPs inhibited cell viability in a dose-dependent manner. The combination of Cis and rGO-AgNPs showed significant effects on cell proliferation, cytotoxicity, and apoptosis. The combination of Cis and rGO-AgNPs had more pronounced effects on the expression of apoptotic and autophagy genes, and also significantly induced the accumulation of autophagosomes and autophagolysosomes, which was associated with the generation of reactive oxygen species.
Our findings substantiated rGO-AgNPs strongly potentiating Cis-induced cytotoxicity, apoptosis, and autophagy in HeLa cells, and hence rGO-AgNPs could be potentially applied to cervical cancer treatment as a powerful synergistic agent with Cis or any other chemotherapeutic agents.
顺铂（Cis）是一种广泛用于治疗多种癌症的化疗药物，因为它能够显著诱导癌细胞死亡。近来，石墨烯及其改性纳米复合材料因其独特的物理化学性质而在癌症治疗中备受关注。本研究的目的是探究顺铂与还原氧化石墨烯-银纳米颗粒纳米复合材料（rGO-AgNPs）在人宫颈癌（HeLa）细胞中的联合效应。
我们使用C-藻蓝蛋白合成了AgNPs、rGO和rGO-AgNP纳米复合材料。使用各种分析技术对合成的纳米材料进行了表征。通过一系列细胞实验评估了顺铂、rGO-AgNPs以及顺铂与rGO-AgNPs组合的抗癌特性，这些实验包括细胞活力、细胞增殖、乳酸脱氢酶泄漏、活性氧生成以及氧化和抗氧化应激标志物（如丙二醛、谷胱甘肽、超氧化物歧化酶和过氧化氢酶）的细胞水平。使用实时逆转录聚合酶链反应测量促凋亡、抗凋亡和自噬基因的表达。
合成的AgNPs分散良好、均匀且呈球形，平均尺寸为10 nm，并均匀分布在石墨烯片上。顺铂、氧化石墨烯（GO）、rGO、AgNPs和rGO-AgNPs均以剂量依赖性方式抑制细胞活力。顺铂与rGO-AgNPs的组合对细胞增殖、细胞毒性和凋亡显示出显著影响。顺铂与rGO-AgNPs的组合对凋亡和自噬基因的表达有更明显的影响，并且还显著诱导了自噬体和自噬溶酶体的积累，这与活性氧的生成有关。
我们的研究结果证实rGO-AgNPs能强烈增强顺铂在HeLa细胞中诱导的细胞毒性、凋亡和自噬，因此rGO-AgNPs作为与顺铂或任何其他化疗药物的强大协同剂，有可能应用于宫颈癌治疗。
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