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Tumor Biology

, Volume 34, Issue 4, pp 2205–2214 | Cite as

Shugoshin1 enhances multidrug resistance of gastric cancer cells by regulating MRP1, Bcl-2, and Bax genes

  • Yafang Wang
  • Lili Liu
  • Xiangqiang Liu
  • Hui Zhang
  • Jiaming Liu
  • Bin Feng
  • Yulong Shang
  • Lin Zhou
  • Kaichun Wu
  • Yongzhan Nie
  • Hongbo Zhang
  • Daiming Fan
Research Article

Abstract

Multidrug resistance (MDR) is a major clinical obstacle in treatment of gastric cancer (GC) and it accounts for the majority of cancer-related mortalities. Shugoshin1 (SGO1) is an important player in appropriate chromosome segregation and is involved in tumorigenesis. In this study, we found endogenous SGO1 overexpression in the multidrug-resistant GC cell lines SGC7901/VCR and SGC7901/ADR compared with their parental cell line SGC7901. By enhancing expression of SGO1, sensitivity of SGC7901 cells to vincristine (VCR), adriamycin, 5-fluorouracil (5-FU), and cisplatin (CDDP) was significantly diminished. Silencing its expression resulted in enhanced sensitivity of SGC7901/VCR and SGC7901/ADR cells to these antitumor drugs. Additionally, we confirmed that SGO1 increased capacity of cells to enable adriamycin (ADR) efflux and inhibit drug-induced apoptosis by regulating MRP 1, Bcl-2, and Bax genes so as to confer a MDR phenotype to GC cells. In brief, these findings suggest that SGO1 promotes MDR of GC cells and may be useful as a novel therapeutic target for preventing or reversing MDR.

Keywords

SGO1 Multidrug resistance Gastric cancer Lentivirus vector 

Abbreviations

SGO1

Shugoshin1

GC

Gastric cancer

MDR

Multidrug resistance

MDR1/P-gp

Multidrug resistance 1/P-glycoprotein

MRP

Multidrug resistance-associated protein

CIN

Chromosomal instability

MTT

3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyl-tetrazolium bromide

Notes

Acknowledgments

This work was supported by the National Nature Science Foundation of China (nos. 81030044 and 81090270).

Conflict of interest

None.

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Copyright information

© International Society of Oncology and BioMarkers (ISOBM) 2013

Authors and Affiliations

  • Yafang Wang
    • 1
  • Lili Liu
    • 2
  • Xiangqiang Liu
    • 1
  • Hui Zhang
    • 1
  • Jiaming Liu
    • 1
  • Bin Feng
    • 1
  • Yulong Shang
    • 1
  • Lin Zhou
    • 1
  • Kaichun Wu
    • 1
  • Yongzhan Nie
    • 1
  • Hongbo Zhang
    • 1
  • Daiming Fan
    • 1
  1. 1.State Key Laboratory of Cancer Biology & Xijing Hospital of Digestive DiseasesFourth Military Medical UniversityXi’anChina
  2. 2.Department of Oncology, Tangdu HospitalFourth Military Medical UniversityXi’anChina

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