Downregulation of GPSM2 is associated with primary resistance to paclitaxel in breast cancer

Oncol Rep. 2020 Mar;43(3):965-974. doi: 10.3892/or.2020.7471. Epub 2020 Jan 17.

Abstract

Paclitaxel is one of the most effective chemotherapy drugs for breast cancer worldwide but 20‑30% patients show primary resistance to the drug. Screening and identification of markers that facilitate effective and rapid prediction of sensitivity to paclitaxel is therefore an urgent medical requirement. In the present study, G protein signaling modulator 2 (GPSM2) mRNA levels were significantly associated with taxane sensitivity in experiments based on the Gene Expression Omnibus (GEO) online database. Immunohistochemical analysis consistently revealed a significant association of GPSM2 protein levels with paclitaxel sensitivity in breast cancer patients. Knockdown of GPSM2 reduced the sensitivity of breast cancer cells to paclitaxel via regulation of the cell cycle. Animal experiments further corroborated our in vitro findings. These results suggest that GPSM2 plays an important role in breast cancer resistance, supporting its utility as a potential target for improving drug susceptibility in patients as well as a marker of paclitaxel sensitivity.

Keywords: breast cancer; GPSM2; paclitaxel; cell cycle.

MeSH terms

  • Aged
  • Animals
  • Antineoplastic Agents, Phytogenic / administration & dosage
  • Breast Neoplasms / drug therapy*
  • Breast Neoplasms / genetics
  • Breast Neoplasms / pathology
  • Bridged-Ring Compounds / administration & dosage
  • Bridged-Ring Compounds / adverse effects
  • Cell Proliferation / drug effects*
  • Drug Resistance, Neoplasm / drug effects
  • Female
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Intracellular Signaling Peptides and Proteins / genetics*
  • MCF-7 Cells
  • Mice
  • Middle Aged
  • Paclitaxel / administration & dosage*
  • Paclitaxel / adverse effects
  • RNA, Messenger / genetics
  • Taxoids / administration & dosage
  • Taxoids / adverse effects
  • Xenograft Model Antitumor Assays

Substances

  • Antineoplastic Agents, Phytogenic
  • Bridged-Ring Compounds
  • GPSM2 protein, human
  • Intracellular Signaling Peptides and Proteins
  • RNA, Messenger
  • Taxoids
  • taxane
  • Paclitaxel