Inhibition of human 67-kDa laminin receptor sensitizes multidrug resistance colon cancer cell line SW480 for apoptosis induction

Tumour Biol. 2016 Jan;37(1):1319-25. doi: 10.1007/s13277-015-3873-5. Epub 2015 Aug 21.

Abstract

The adhesion mediated drug resistance in cancer cells resulted from adhesion of the extracellular matrix is a major cause for multidrug resistance (MDR) and leads chemotherapeutic failure for colon cancer. In this study, we explored the role of 67-kDa laminin receptor (67LR) in chemotherapeutic drug resistance in colon cancer cells. SiRNA-mediated knockdown of 67LR decreased the cell adhesion when laminins were applied. Moreover, 67LR knockdown increased the expression of pro-apoptotic gene Bax but inhibited the expression of anti-apoptotic gene Bcl-2. Enhanced apoptosis was observed in 67LR siRNA-transfected SW480 cell when the cell was treated with doxorubicin for apoptosis induction. Furthermore, MTT assay revealed that the IC50 of chemotherapeutic toward SW480 cell adhesion to laminins was reduced after 67LR knockdown, indicating there was a significant increase of drug sensitivity in SW480 cell. In conclusion, our study demonstrated that 67LR plays a considerable role in the development of colon cancer MDR.

Keywords: Adhesion; Apoptosis; CMDR; Colon cancer; Laminin.

MeSH terms

  • Antineoplastic Agents / therapeutic use
  • Apoptosis*
  • Cell Adhesion
  • Cell Line, Tumor / drug effects
  • Cisplatin / administration & dosage
  • Colonic Neoplasms / metabolism*
  • Colonic Neoplasms / pathology
  • Drug Resistance, Multiple*
  • Drug Resistance, Neoplasm*
  • Extracellular Matrix / metabolism
  • Fluorouracil / administration & dosage
  • Gene Expression Regulation, Neoplastic*
  • Humans
  • Inhibitory Concentration 50
  • Laminin / chemistry
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • RNA Interference
  • RNA, Small Interfering / metabolism
  • Receptors, Laminin / metabolism
  • Ribosomal Proteins

Substances

  • Antineoplastic Agents
  • BCL2 protein, human
  • Laminin
  • Proto-Oncogene Proteins c-bcl-2
  • RNA, Small Interfering
  • RPSA protein, human
  • Receptors, Laminin
  • Ribosomal Proteins
  • Cisplatin
  • Fluorouracil