Knockdown of LRP/LR induces apoptosis in pancreatic cancer and neuroblastoma cells through activation of caspases

Exp Cell Res. 2017 Nov 15;360(2):264-272. doi: 10.1016/j.yexcr.2017.09.016. Epub 2017 Sep 10.

Abstract

The 37kDa/67kDa laminin receptor (LRP/LR) serves various physiological and pathological roles such as enhancing tumour-related processes including metastasis, angiogenesis, cellular viability and telomerase activation in cancerous cell lines. The present study investigates the effect of siRNA mediated downregulation of LRP/LR on pancreatic cancer (AsPC-1) and neuroblastoma (IMR-32) cells. MTT and BrdU assays revealed that siRNA mediated downregulation of LRP resulted in a significant reduction in cell viability and cell proliferation. In addition, knock-down of LRP resulted in phosphatidylserine externalization, diminished nuclear integrity and significantly enhanced caspase-3 activity, which is indicative of apoptosis. LRP downregulation resulted in a significant increase in caspase-8 activity in IMR-32 cells and enhanced caspase-8 and 9 activity in AsPC-1 cells. These data recommend siRNA mediated knock-down of LRP as a potential therapeutic avenue for the treatment of pancreatic cancer and neuroblastoma.

Keywords: 37kDa/67kDa laminin Receptor; Apoptosis; Neuroblastoma; Pancreatic cancer; Small interfering RNAs.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Apoptosis / drug effects
  • Apoptosis / genetics*
  • Caspases / metabolism*
  • Enzyme Activation / drug effects
  • Enzyme Activation / genetics
  • Gene Expression Regulation, Neoplastic / drug effects
  • Gene Knockdown Techniques
  • Humans
  • Neuroblastoma / genetics*
  • Neuroblastoma / pathology
  • Pancreatic Neoplasms / genetics*
  • Pancreatic Neoplasms / pathology
  • RNA, Small Interfering / pharmacology
  • Receptors, Laminin / genetics*
  • Tumor Cells, Cultured

Substances

  • RNA, Small Interfering
  • Receptors, Laminin
  • Caspases