Int J Med Sci 2019; 16(12):1541-1548. doi:10.7150/ijms.37427 This issue
1. Department of Hepatobiliary and Pancreatic Surgery, the First Hospital, Jilin University, Jilin 130021, China;
2. Edmond H. Fischer Signal Transduction Laboratory, School of Life Sciences, Jilin University, Changchun, Jilin 130012, China.
*Hongqiao Cai, Yang Yang and Fenghui Peng contributed equally to this manuscript.
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-miR221 on HCC cell lines.
Methods: 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 in vitro 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.
Results: AuNPs-anti-miR221 can enhance the effect of sorafenib in inhibiting cell proliferation via inactivating miR-221/p27/DNMT1 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.
Keywords: hepatocellular carcinoma, sorafenib, gold nanoparticles, miR-221, signaling pathway