Quercetin shows anti-tumor effect in hepatocellular carcinoma LM3 cells by abrogating JAK2/STAT3 signaling pathway

Cancer Med. 2019 Aug;8(10):4806-4820. doi: 10.1002/cam4.2388. Epub 2019 Jul 5.

Abstract

Objective: Hepatocellular carcinima is one of the most common tumors in clinic and also one of the leading causes of death from cancer worldwide. Quercetin shows significant effects on blocking the development of various cancers.

Methods: We used the human hepatocellular carcinoma LM3 and nude mice tumor model to assess the effects of quercetin in hepatocellular carcinoma and clarify its mechanism of action. We collected LM3 cell line treated with different doses of quercetin at different time periods and determined the vital indexes. The liver tissues of mice were collected and used for western boltting (WB), Hematoxylin and Eosin (H&E) and TUNEL staining.

Results: Results indicated that quercetin suppressed the Hepatocellular carcinoma (HCC) growth both in vivo and in vitro. Quercetin could disturb LM3 cells proliferation and cell cycle distribution, thus inducing apoptosis. At the same time, quercetin inhibited LM3 cells migration and invasion and promoted HCC autophagy. These effects at least partly depended on the down-regulation of the activation of JAK2 and STAT3 by quercetin.

Conclusion: Quercetin inhibited hepatocellular carcinoma progression by modulating cell apoptosis, migration, invasion, and autophagy; and its effects were at least partly related with the JAK2/STAT3 signaling pathway.

Keywords: JAK2/STAT3 pathway; apoptosis; autophagy; hepatocellular carcinoma; metastasis; quercetin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / administration & dosage*
  • Antineoplastic Agents / pharmacology
  • Carcinoma, Hepatocellular / drug therapy*
  • Carcinoma, Hepatocellular / metabolism
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Janus Kinase 2 / metabolism
  • Liver Neoplasms / drug therapy*
  • Liver Neoplasms / metabolism
  • Mice
  • Mice, Nude
  • Quercetin / administration & dosage*
  • Quercetin / pharmacology
  • STAT3 Transcription Factor / metabolism
  • Signal Transduction / drug effects*
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents
  • STAT3 Transcription Factor
  • STAT3 protein, human
  • Quercetin
  • JAK2 protein, human
  • Janus Kinase 2