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Reversion of Multidrug Resistance by SKI-II in SGC7901/DDP Cells and Exploration of Underlying Mechanisms

  • Zhu, Zu-An (Department of Gastroenterology, Affiliated Hospital of Xuzhou Medical College) ;
  • Zhu, Zheng-Qiu (Department of Medical Oncology, Affiliated Hospital of Xuzhou Medical College) ;
  • Cai, Hong-Xing (Department of Forensic Medicine, Yancheng Health Professional Technology Institute) ;
  • Liu, Ying (Department of Pathology, Xuzhou Medical College)
  • Published : 2012.02.29

Abstract

In order to investigate whether SKI-II could reverse drug resistance and its possible mechanisms, we treated SGC7901/DDP cells with SKI-II or SKI-II in combination with DDP. Then cell growth, apoptosis, micromorphological changes, and expression of SphK1, P-gp, NF-${\kappa}B$, Bcl-2 and Bax were assessed by MTT assay, flow cytometry, electron microscopy, immunocytochemistry and Western blot assay respectively. SGC7901/DDP cells were insensitive to cisplatin 2.5mg/L, but when pretreated with SKI-II, their proliferation was inhibited by cisplatin 2.5mg/L significantly, the inhibition rate increasing with time and dose. The apoptosis rate was also significantly elevated. Expression of SphK1 and P-gp was decreased significantly, Pearson correlation analysis showing significant correlation between the two (r=0.595, P<0.01). Expression of NF-${\kappa}B$ and Bcl-2 was decreased significantly,while that of Bax was increased, compared to the control group. There were significant correlations between SphK1 and NF-${\kappa}B$(r=0.723, P<0.01), NF-${\kappa}B$ and Bcl-2(r=0.768, P<0.01). All these data indicated that SKI-II could reverse drug resistance of SGC7901/DDP to cisplatin by down-regulating expression of P-gp and up-regulating apoptosis through down-regulation of SphK1. The increased apoptotic sensitivity of SGC7901/DDP to cisplatin was due to the decreasing proportion of Bcl-2/Bax via down-regulating NF-${\kappa}B$.

Keywords

SGC7901/DDP cells;resistance;SKI-II;apoptosis;SphK1

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