Heat Shock Protein 27, a Novel Regulator of Transforming Growth Factor β Induced Resistance to Cisplatin in A549 Cell

Pharmacology. 2017;100(5-6):283-291. doi: 10.1159/000479320. Epub 2017 Aug 19.

Abstract

Lung cancer is one of the major causes of cancer morbidity and mortality around the world, and the resistance to cisplatin is a critical issue to chemotherapy in lung cancer patients. Transforming growth factor β (TGF-β) signal pathway abnormality is widely observed in drug resistance during lung cancer chemotherapy. Here, we investigated the effects of heat-shock protein 27 (HSP27) in the TGF-β-induced cisplatin resistance in lung cancer cell. In this study, our results indicated that the mRNA and protein expression of HSP27 were significantly increased in human lung cancer tissues. TGF-β induced the mRNA and protein expression of HSP27 in human lung cancer cell (A549). Treatment of TGF-β-induced cisplatin resistance in A549 cell through blocking the cisplatin-induced apoptosis and cell death, which characterized as the increasing of cell viability and decreasing of PARP and caspase3 cleavage in the cisplatin-treated cell. Knockdown of SMAD3 attenuated the TGF-β-induced HSP27 expression and restored the TGF-β-induced cisplatin resistance in A549 cell. Additionally, the knockdown of HSP27 blocked TGF-β-induced cisplatin resistance via decreasing cell viability and increasing cell apoptosis in A549 cell. These data therefore suggested that HSP27 is critical to lung cancer progression and TGF-β-induced cisplatin resistance in human lung cancer cell, and may provide an effective clinical strategy in lung cancer patients with resistance to chemotherapy.

Keywords: A549 cell; Cisplatin; Heat-shock protein 27; Lung cancer; Transforming growth factor β.

MeSH terms

  • A549 Cells
  • Apoptosis / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / physiology*
  • HSP27 Heat-Shock Proteins / metabolism*
  • Heat-Shock Proteins
  • Humans
  • Lung Neoplasms / drug therapy*
  • Lung Neoplasms / metabolism*
  • Molecular Chaperones
  • RNA, Messenger / metabolism
  • Signal Transduction / drug effects
  • Transforming Growth Factor beta / metabolism*

Substances

  • HSP27 Heat-Shock Proteins
  • HSPB1 protein, human
  • Heat-Shock Proteins
  • Molecular Chaperones
  • RNA, Messenger
  • Transforming Growth Factor beta
  • Cisplatin