The Synergistic Cytotoxic Effect of Laser-Irradiated Gold Nanoparticles and Sorafenib Against the Growth of a Human Hepatocellular Carcinoma Cell Line

Asian Pac J Cancer Prev. 2019 Nov 1;20(11):3369-3376. doi: 10.31557/APJCP.2019.20.11.3369.

Abstract

Gold nanoparticles are the most promising candidate in cancer treatment due to their physiochemical properties<br /> and increased use in photothermal therapy (PTT). In the present study, spherical gold nanoparticles (AuNPs) were<br /> synthesized using citrate reduction method. The particles were then characterized using UV-VIS spectroscopy and<br /> transmission electron microscope. A hepatocellular carcinoma cell line (HepG2) was incubated with sorafenib and/or<br /> non-irradiated or laser-irradiated AuNPs for 48 hrs. The cytotoxic effect of different treatment modalities was determined<br /> using MTT assay. Furthermore, apoptosis was determined by flow cytometry using annexin V/propidium iodide, as<br /> well as estimating the level of caspases. Results showed that AuNPs and sorafenib reduced HepG2 cell viability, and<br /> the cytotoxicity was associated with increased release of LDH in the culture medium. The recorded cytotoxicity was<br /> attributed to enhanced apoptosis as revealed by increased cellular caspases (3, 8 and 9), that was further confirmed by<br /> flow cytometry. The most notable cytotoxic effect was recorded when combining sorafenib with laser-irradiated AuNPs.<br /> In conclusion, a synergistic cytotoxic effect was observed between sorafenib and laser-irradiated AuNPs against the<br /> growth of HepG2, suggesting the potential substitution of large toxic doses of sorafenib by lower doses in combination<br /> with photothermal therapy.

Keywords: Gold Nanoparticles; Hepatocellular carcinoma; photothermal therapy; sorafenib.

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Caspases / metabolism
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Cell Survival / drug effects
  • Drug Synergism
  • Gold / administration & dosage*
  • Hep G2 Cells
  • Humans
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Metal Nanoparticles / administration & dosage*
  • Sorafenib / pharmacology*

Substances

  • Antineoplastic Agents
  • Gold
  • Sorafenib
  • Caspases