Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Jilin 130021, China.
Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, Jilin 130012, China.
Int J Med Sci. 2019 Oct 21;16(12):1541-1548. doi: 10.7150/ijms.37427. eCollection 2019.
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-miR221 on HCC cell lines. Gold nanoparticles-loaded anti-miR221 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-miR221 alone or combination to investigate the inhibitory effect by CCK-8, live/dead fluorescence staining and colony-forming unit assays. MiR-221/p27/DNMT1 signaling pathway including p27 and DNMT1 was examined by western blot. AuNPs-anti-miR221 can enhance the effect of sorafenib in inhibiting cell proliferation via inactivating miR-221/p27/DNMT1 signaling pathway. 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.
目前，索拉非尼是治疗肝细胞癌（HCC）晚期的主要系统化疗药物。然而，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 中发挥促进肿瘤发生的作用。在本研究中，我们分析了索拉非尼和载金纳米粒抗 miR221 联合对 HCC 细胞系的协同抗肿瘤作用。通过透射电子显微镜、紫外-可见光谱、Zeta 电位和动态光散射测量以及共聚焦显微镜和暗场成像研究和鉴定了载金纳米粒抗 miR221。用索拉非尼和 AuNPs-anti-miR221 单独或联合处理两种 HCC 细胞系，通过 CCK-8、活/死荧光染色和集落形成单位测定来研究抑制作用。通过 Western blot 检测 miR-221/p27/DNMT1 信号通路，包括 p27 和 DNMT1。AuNPs-anti-miR221 可以通过失活 miR-221/p27/DNMT1 信号通路增强索拉非尼抑制细胞增殖的作用。我们的结果表明，索拉非尼联合 AuNPs-anti-miR221 治疗确实可以协同有效地抑制 HCC 细胞系的增殖。这些数据表明，AuNPs-anti-miR221 可能是索拉非尼治疗 HCC 的一种有前途的化疗增敏剂。
