Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating lncRNA AK022798 expression

Anticancer Drugs. 2015 Jul;26(6):632-40. doi: 10.1097/CAD.0000000000000227.

Abstract

Gastric cancer is now the fourth most common malignancy and the second leading cause of death because of cancer. The resistance to anticancer drugs is the main cause of chemotherapy failure. In this study, we explored the role of Notch 1 and long noncoding RNA (lncRNA) in drug-resistant gastric cancer formation. First, we found that Notch 1 was highly expressed in the cisplatin-resistant gastric cancer cell lines SGC7901/DDP and BGC823/DDP cells. Then, we constructed a Notch 1 overexpression vector plasmid; after successful transfection, the SGC7901 and BGC823 cells highly expressed Notch 1. Moreover, the expression of multidrug resistance-associated protein 1 (MRP1), P-glycoprotein, increased significantly and the apoptosis of SGC7901 and BGC823 cells obviously reduced. We further screened out the lncRNA AK022798 involved in this process. Furthermore, we used siRNA to interfere with lncRNA AK022798 expression, and found that the expression of MRP1 and P-glycoprotein decreased significantly in SGC7901/DDP and BGC823/DDP cells, and their apoptosis as well as the expressions of caspase 3 and caspase 8 obviously increased. These results suggest that Notch 1 can promote the lncRNA AK022798 expression and result in the formation of SGC7901/DDP and BGC823/DDP cells. It may provide a new, useful method for gastric cancer chemotherapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / pharmacology*
  • Apoptosis / genetics
  • Cell Line, Tumor
  • Cell Proliferation / genetics
  • Cisplatin / pharmacology*
  • Drug Resistance, Neoplasm / genetics
  • Humans
  • RNA, Long Noncoding / metabolism*
  • Receptor, Notch1 / genetics
  • Receptor, Notch1 / metabolism*
  • Stomach Neoplasms / pathology*
  • Up-Regulation

Substances

  • Antineoplastic Agents
  • NOTCH1 protein, human
  • RNA, Long Noncoding
  • Receptor, Notch1
  • Cisplatin