Morphine may act via DDX49 to inhibit hepatocellular carcinoma cell growth

Aging (Albany NY). 2021 May 5;13(9):12766-12779. doi: 10.18632/aging.202946. Epub 2021 May 5.

Abstract

Pain in hepatocellular carcinoma (HCC) is a frequent cause of low quality of life, and morphine is routinely used as a first-line opiate analgesic in HCC. Morphine may exert not only analgesic effects but also anti-cancer effects via unknown mechanisms. Here we show that morphine can inhibit HCC cell proliferation. We further show that DEAD-box helicase 49 (DDX49) is up-regulated in HCC tumors, and that knocking down the DDX49 gene decreases tumor formation in vivo and in vitro, as well as reduces tumor metastasis in vivo. Morphine decreases DDX49 expression in HCC cells. Our results suggest that DDX49 contributes to HCC, and that morphine may exert anti-cancer effects by down-regulating it.

Keywords: DDX49; anti-cancer; hepatocellular carcinoma; morphine.

Publication types

  • Observational Study
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Animals
  • Apoptosis / drug effects
  • Apoptosis / genetics
  • Cancer Pain / drug therapy*
  • Cancer Pain / etiology
  • Carcinoma, Hepatocellular / complications
  • Carcinoma, Hepatocellular / pathology
  • Carcinoma, Hepatocellular / therapy*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Chemotherapy, Adjuvant / methods
  • DEAD-box RNA Helicases / antagonists & inhibitors
  • DEAD-box RNA Helicases / genetics*
  • Dose-Response Relationship, Drug
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Hepatectomy
  • Humans
  • Liver / pathology
  • Liver / surgery
  • Liver Neoplasms / complications
  • Liver Neoplasms / pathology
  • Liver Neoplasms / therapy*
  • MAP Kinase Signaling System / drug effects
  • MAP Kinase Signaling System / genetics
  • Male
  • Mice
  • Middle Aged
  • Morphine / pharmacology*
  • Morphine / therapeutic use
  • Xenograft Model Antitumor Assays

Substances

  • Morphine
  • DDX49 protein, human
  • DEAD-box RNA Helicases