Human mitochondrial Mrs2 protein promotes multidrug resistance in gastric cancer cells by regulating p27, cyclin D1 expression and cytochrome C release

被引：30

作者：

Chen, Yu ^{[1
,2
]}

Wei, Xufeng ^{[3
]}

Yan, Pengfei ^{[1
,2
]}

Han, Ying ^{[1
,2
]}

Sun, Shiren ^{[1
,2
]}

Wu, Kaichun ^{[1
,2
]}

Fan, Daiming ^{[1
,2
]}

机构：

[1] Fourth Mil Med Univ, State Key Lab Canc Biol, Xijing Hosp, Xian 710032, Shaanxi Prov, Peoples R China

[2] Fourth Mil Med Univ, Inst Digest Dis, Xijing Hosp, Xian 710032, Shaanxi Prov, Peoples R China

[3] Fourth Mil Med Univ, Dept Cardiovasc Surg, Xijing Hosp, Xian 710032, Shaanxi Prov, Peoples R China

来源：

CANCER BIOLOGY & THERAPY | 2009年 / 8卷 / 07期

关键词：

human mitochondrial Mrs2 protein; gastric cancer; drug resistance; cell cycle; apoptosis; PERMEABILITY TRANSITION PORE; P-GLYCOPROTEIN; TUMOR-CELLS; MAGNESIUM; GENE; LOCALIZATION; APOPTOSIS; GROWTH; SENSITIVITY; PATHWAY;

D O I：

10.4161/cbt.8.7.7920

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Human mitochondrial Mrs2 protein (hsaMrs2p) is a magnesium transporter in mitochondria inner membrane. It was identified as an upregulated gene in a multidrug-resistant (MDR) gastric cancer cell line compared to its parental cells by subtractive hybridization. To further explore the role of hsaMrs2p in MDR of gastric cancer cells, the cDNA encoding hsaMrs2p was generated and mouse antisera against hsaMrs2p was raised with recombinant hsaMrs2p as the immunogen. HsaMrs2p expression could positively regulate adriamycin resistance of SGC7901/ADR cells both in vitro and in vivo. Further study showed that hsaMrs2p increased adriamycin-releasing index. Its upregulation inhibited adriamycin-induced apoptosis, probably by suppressing Bax induced cytochrome C release from mitochondria. Additionally, hsaMrs2p promoted cell growth and cells with decreased hsaMrs2p exhibited significant inhibition of cell growth with G(1) cell cycle arrest. By enhanced hsaMrs2p expression, p27 was downregulated whereas cyclinD1 was upregulated. Our results provide new insights into the function of hsaMrs2p that may be a promising target for MDR reversal therapy.

引用

页码：607 / 614

页数：8

共 38 条

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