Gold nanoparticles-loaded anti-miR22l enhances antitumor effect of sorafenib in hepatocellular carcinoma cells
Gold nanoparticles-loaded anti-miR22l enhances antitumor effect of sorafenib in hepatocellular carcinoma cells
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DOI：
10.7150/ijms.37427
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发表时间：
2019-01-01
影响因子：
3.6
通讯作者：
Ji, Bai
中科院分区：
文献类型：
--
作者：
Cai, Hongqiao;Yang, Yang;Ji, Bai
目的：索拉非尼是目前治疗中晚期肝癌的主要全身化疗药物。然而，来自一些临床HCC患者的新数据表明，索拉非尼单独使用仅具有中等的抗肿瘤疗效，并且不能抑制疾病的转移和进展。miR-221通过抑制p27的表达在HCC中起促进肿瘤发生的作用。方法：采用透射电镜、紫外-可见光谱、动态光散射、共聚焦显微镜和暗场成像等方法，对载金抗miR 22 l纳米颗粒与索拉非尼协同抗肝癌作用进行研究。采用CCK-8、活/死荧光染色和集落形成单位测定法，观察索拉非尼和AuNPs-anti-miR 221单独或联合作用对肝癌细胞系的抑制作用。结果：AuNPs-anti-miR 221可通过抑制miR-221/p27/DNMTI信号通路增强索拉非尼对肝癌细胞增殖的抑制作用。结论：索拉非尼联合AuNPs-anti-miR 221可协同抑制肝癌细胞增殖。这些数据表明AuNP-抗miR 221可能是索拉非尼治疗HCC的有希望的化疗增敏剂。
Objective: Currently, sorafenib is the main systemic chemotherapy drug for advanced stage of hepatocellular carcinoma (HCC). However, emerging data from some clinical HCC patients indicates that sorafenib alone has only moderate antitumor efficacy, and could not inhibit metastasis and progression of disease. MiR-221 plays a role in promoting tumorigenesis in HCC by inhibiting the expression of p27. In this study, we analyzed the synergistic anti-tumor effects of sorafenib and gold nanoparticles-loaded anti-miR22l on HCC cell lines.Methods: Gold nanoparticles-loaded anti-miR22l was investigated and identified by transmission electron microscope, ultraviolet-visible spectroscopy, zeta potential and dynamic light scattering measurements as well as the confocal microscopy and dark-field imaging. Two HCC cell lines were treated with sorafenib and AuNPs-anti-miR22l alone or combination in vitro to investigate the inhibitory effect by CCK-8, live/dead fluorescence staining and colony-forming unit assays. MiR-221/p27/DNMTI signaling pathway including p27 and DNMT I was examined by western blot.Results: AuNPs-anti-miR22l can enhance the effect of sorafenib in inhibiting cell proliferation via inactivating miR-221/p27/DNMTI signaling pathway.Conclusions: Our results demonstrate that sorafenib combined with AuNPs-anti-miR221 treatment does effectively inhibit proliferation of HCC cell lines synergistically. These data suggest the AuNPs-anti-miR221 may be a promising chemosensitizer to sorafenib in the treatment of HCC.