Insulin-like growth factor 1 inhibits autophagy of human colorectal carcinoma drug-resistant cells via the protein kinase B/mammalian target of rapamycin signaling pathway

Mol Med Rep. 2018 Feb;17(2):2952-2956. doi: 10.3892/mmr.2017.8272. Epub 2017 Dec 12.

Abstract

Insulin-like growth factor 1 (IGF-1) is reported to inhibit autophagy of human colorectal carcinoma cells (HCT); however, little is known regarding the mechanisms underlying the inhibitory effect of IGF-1 on autophagy in HCT resistant strains. The present study aimed to analyze the inhibitory effect of IGF-1 on the autophagy of HCT resistant strains and its potential underlying mechanisms. The viability and apoptosis of HCT-8 colon cancer cells were analyzed, and expression levels of relevant genes and proteins were investigated using reverse transcription-quantitative polymerase chain reaction and western blot analysis, respectively. Treatment of cells with IGF-1 induced apoptosis. IGF-1 treatment activated protein kinase B (AKT), which may inhibit autophagy via the AKT/mammalian target of rapamycin signaling pathway. Following inhibition of autophagy, drug resistant cells became sensitive to apoptosis induced by 5-fluorouracil.

MeSH terms

  • Antimetabolites, Antineoplastic / pharmacology
  • Apoptosis / drug effects
  • Autophagy* / drug effects
  • Cell Line, Tumor
  • Colorectal Neoplasms / drug therapy
  • Colorectal Neoplasms / metabolism*
  • Drug Resistance, Neoplasm
  • Fluorouracil / pharmacology
  • Humans
  • Insulin-Like Growth Factor I / metabolism*
  • Proto-Oncogene Proteins c-akt / metabolism*
  • Signal Transduction* / drug effects
  • TOR Serine-Threonine Kinases / metabolism*

Substances

  • Antimetabolites, Antineoplastic
  • IGF1 protein, human
  • Insulin-Like Growth Factor I
  • TOR Serine-Threonine Kinases
  • Proto-Oncogene Proteins c-akt
  • Fluorouracil