Polysaccharides Produced by the Mushroom Trametes robiniophila Murr Boosts the Sensitivity of Hepatoma Cells to Oxaliplatin via the miR-224-5p/ABCB1/P-gp Axis

Integr Cancer Ther. 2022 Jan-Dec:21:15347354221090221. doi: 10.1177/15347354221090221.

Abstract

Aim: To investigate the mechanisms employed by PS-T (polysaccharides of Trametes, PS-T), the main active ingredient of Huaier granules, to improve the susceptibility of hepatoma cells to oxaliplatin (OXA).

Methods: Cell proliferation in response to PS-T was determined both in vitro and in vivo. The effects of PS-T on miRNAs were analyzed with the use of a microarray. MiRNAs were screened under specific conditions (P < .05, logFoldChange > ABS [1.5]) and further silenced or overexpressed by liposome transfection. Levels of ABCB1 mRNA and P-gp were detected by qRT-PCR and western blot analysis, respectively. A dual fluorescence assay was performed to determine whether miRNA directly targets ABCB1.

Results: PS-T enhanced the inhibitory effect of OXA in human hepatoma cells and xenografts. Among 5 up-regulated miRNAs, overexpression of only miR-224-5p inhibited the expression of ABCB1 mRNA and P-gp, while silencing of miR-224-5p had an opposite effect. Moreover, miR-224-5p can directly target the 3'-UTR of ABCB1.

Conclusion: PS-T increases the sensitivity of human hepatoma cells to OXA via the miR-224-5p/ABCB1/P-gp axis.

Keywords: Trametes robiniophila Murr; chemotherapy resistance; hepatocellular carcinoma; miR-224-5p; microRNA array.

MeSH terms

  • ATP Binding Cassette Transporter, Subfamily B / genetics
  • Agaricales*
  • Carcinoma, Hepatocellular* / metabolism
  • Cell Line, Tumor
  • Cell Proliferation
  • Drug Resistance, Neoplasm
  • Humans
  • Liver Neoplasms* / metabolism
  • MicroRNAs* / genetics
  • MicroRNAs* / metabolism
  • Oxaliplatin / pharmacology
  • Polyporaceae
  • Polysaccharides / pharmacology
  • RNA, Messenger / genetics
  • Trametes / genetics
  • Trametes / metabolism

Substances

  • ABCB1 protein, human
  • ATP Binding Cassette Transporter, Subfamily B
  • MIRN224 microRNA, human
  • MicroRNAs
  • Polysaccharides
  • RNA, Messenger
  • Oxaliplatin

Supplementary concepts

  • Trametes robiniophila