49. Midkine confers adriamycin resistance in human gastric cancer cells

Background: Midkine (MDK) is a heparin-binding molecule involved in the regulation of growth and differentiation during embryogenesis, which is overexpressed in most of human malignant tumors and may act as an oncogene. The aim of the current study was to investigate the mechanism of MDK involved in the Adriamycin (ADR) resistance in human gastric cancer cells in vitro.
Methods: SGC7901 gastric cancer cell line and Adriamycinresistant SGC7901 (SGC7901/ADR) were used to investigate the mechanism of MK affect on the ADR resistance in gastric cancer cells. Cell lines were stably transfected with human MDK cDNA. Cells viability was determined by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. Quantitative Real-time PCR and Western Blot were used to examine the expression of mRNA and Protein.
Results: MDK mRNA and protein expression levels were significantly higher in SGC7901/ADR than in SGC7901. Multidrug resistance type I (MDR1) was found in SGC7901/ ADR, not in SGC7901 by RT-PCR and Western Blot regardless of MDK transfection. We also showed the upregulation of phosphorylated protein kinase B (AKT) and phosphorylated extracellular signalregulated protein kinase (ERK) in Adriamycin-sensitive SGC7901 cell by MDK transfection accompanied with drug resistance to ADR, although the level of AKT and ERK protein expression did not change.
Conclusions: Our results suggested that MDK, which can activate AKT and ERK by phosphorylation, induced the Adriamycin resistance in gastric cancer cells. Understanding the molecular mechanisms, driving MDK-induced ADR resistance, will provide benefits in developing new therapies for gastric cancer.