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Tumor Biology
Published in: Tumor Biology 3/2010

01-06-2010 | Research Article

Depression of MAD2 inhibits apoptosis and increases proliferation and multidrug resistance in gastric cancer cells by regulating the activation of phosphorylated survivin

Authors: Li Wang, Fang Yin, Yulei Du, Bei Chen, Shuhui Liang, Yongguo Zhang, Wenqi Du, Kaichun Wu, Jie Ding, Daiming Fan

Published in: Tumor Biology | Issue 3/2010

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Abstract

Mitotic arrest-deficient 2 (MAD2) is one of the essential mitotic spindle checkpoint regulators, and it can protect cells from aberrant chromosome segregation. The Mad2 gene is very rarely mutated in many kinds of human cancer, but aberrantly reduced expression of MAD2 has been correlated with defective mitotic checkpoints in several human cancers. We have previously found that the MAD2 expression level is also shown to be associated with the multidrug resistance of tumour cells. In this study, we constructed a small interfering RNA (siRNA) eukaryotic expression vector of MAD2 and downregulated MAD2 expression in the gastric cancer cell line SGC7901 by transfection of MAD2-siRNA. SGC7901 cells stably transfected with the MAD2-siRNA exhibited significantly increased expression of phosphorylated survivin protein and enhanced drug resistance. Furthermore, MAD2-siRNA suppressed the proliferation of SGC7901 cells and inhibited tumour formation in athymic nude mice. This study clearly reveals that downregulation of MAD2 could regulate the cell cycle, increase proliferation, and improve the drug resistance of gastric cancer cells by regulating the activation of phosphorylated survivin. It also suggests both that MAD2 might play an important role in the development of human gastric cancer and that silencing the MAD2 gene may help to deal with the multidrug resistance of gastric cancer cells.
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Metadata
Title
Depression of MAD2 inhibits apoptosis and increases proliferation and multidrug resistance in gastric cancer cells by regulating the activation of phosphorylated survivin
Authors
Li Wang
Fang Yin
Yulei Du
Bei Chen
Shuhui Liang
Yongguo Zhang
Wenqi Du
Kaichun Wu
Jie Ding
Daiming Fan
Publication date
01-06-2010
Publisher
Springer Netherlands
Published in
Tumor Biology / Issue 3/2010
Print ISSN: 1010-4283
Electronic ISSN: 1423-0380
DOI
https://doi.org/10.1007/s13277-010-0036-6

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