Effect of Combined Sorafenib/Cisplatinum Treatment on the Autophagy and Proliferation of Hepatocellular Carcinoma hepG2 Cells in Vitro

Asian Pac J Cancer Prev. 2020 Oct 1;21(10):2853-2857. doi: 10.31557/APJCP.2020.21.10.2853.

Abstract

Objective: To explore the effect of combined Sorafenib/ cisplatinum treatment on the autophagy and proliferation of hepatocellular carcinoma (HepG2) cells in vitro.

Methods: HepG2 cells were cultured and treated with different concentrations of Sorafenib, cisplatinum, or a combination of both over a 24-hour period. Cell proliferation was evaluated using a CCK8 assay, and the mRNA expression of the autophagy-related proteins AKT, mTOR, and LC3 were detected using quantitative PCR (qPCR). AKT, pAKT (Ser473), mTOR, pmTOR (Ser2448), LC3I, and LC3II protein expression levels were evaluated by western blot.

Results: We found that the survival rate of HepG2 cells was 47.42% when treated with Sorafenib (10 μmol/L) monotherapy, and 46.04% when treated with cisplatinum (10 mg/L) monotherapy. When Sorafenib(10 μmol/L) was combined with cisplatinum (10 mg/L), the cellular proliferation and survival rate was only 16.71% ( P <0.05). qPCR and western blot revealed that a combination of Sorafenib (10 μmol/L) and cisplatinum (10 mg/L) reduced the transcription and protein expression of autophagy-related AKT and mTOR but increased that of LC3 (P <0.05).

Conclusion: Combining Sorafenib and cisplatinum can effectively induce cell autophagy and reduce cellular proliferation via the PI3K/AKT/mTOR signal pathway.<br />.

Keywords: Autophagy; Hepatocellular carcinoma; Key words: Sorafenib; cis-platinum.

MeSH terms

  • Antineoplastic Combined Chemotherapy Protocols / pharmacology*
  • Apoptosis
  • Autophagy*
  • Carcinoma, Hepatocellular / drug therapy
  • Carcinoma, Hepatocellular / metabolism
  • Carcinoma, Hepatocellular / pathology*
  • Cell Proliferation*
  • Cisplatin / administration & dosage
  • Hep G2 Cells
  • Humans
  • In Vitro Techniques
  • Liver Neoplasms / drug therapy
  • Liver Neoplasms / metabolism
  • Liver Neoplasms / pathology*
  • Proto-Oncogene Proteins c-akt / metabolism
  • Signal Transduction
  • Sorafenib / administration & dosage
  • TOR Serine-Threonine Kinases / metabolism

Substances

  • Sorafenib
  • MTOR protein, human
  • Proto-Oncogene Proteins c-akt
  • TOR Serine-Threonine Kinases
  • Cisplatin