Targeting superoxide dismutase 1 to overcome cisplatin resistance in human ovarian cancer

被引：50

作者：

Brown, Dawn P. G. ^{[2
]}

Chin-Sinex, Helen ^{[3
]}

Nie, Bei ^{[2
]}

Mendonca, Marc S. ^{[3
,4
]}

Wang, Mu ^{[1
,2
,5
]}

机构：

[1] Indiana Univ, Biotechnol Res & Training Ctr, Indianapolis, IN 46202 USA

[2] Indiana Univ Sch Med, Dept Biochem & Mol Biol, Indianapolis, IN 46202 USA

[3] Indiana Univ Sch Med, Dept Radiat Oncol, Indianapolis, IN 46202 USA

[4] Indiana Univ Sch Med, Dept Med & Mol Genet, Indianapolis, IN 46202 USA

[5] Monarch LifeSci, Indianapolis, IN 46202 USA

来源：

CANCER CHEMOTHERAPY AND PHARMACOLOGY | 2009年 / 63卷 / 04期

关键词：

Ovarian cancer; Cisplatin resistance; Superoxide dismutase 1; Reactive oxygen species; Mass spectrometry; OXIDATIVE STRESS; GLUTATHIONE; INHIBITION; APOPTOSIS; CELLS; OVEREXPRESSION; THIOREDOXIN; TOXICITY; DNA;

D O I：

10.1007/s00280-008-0791-x

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Purpose Clinical drug resistance to platinum-based chemotherapy is considered a major impediment in the treatment of human ovarian cancer. Multiple pathways associated with drug resistance have been suggested by many previous studies. Over expression of several key proteins involved in DNA repair, drug transport, redox regulation, and apoptosis has been recently reported by our group using a global quantitative proteomic profiling approach. Superoxide dismutase 1 (SOD1) is one of these proteins consistently over-expressed in cisplatin-resistant ovarian cancer cells as compared to their sensitive counterparts, but its precise role in drug resistance is yet to be defined. Method In the current study, we examined the role of SOD1 in drug resistance by inhibiting its redox activity in cisplatin-resistant ovarian cancer cells using a small-molecule inhibitor, triethylenetetramine (TETA). The effect of TETA was determined by the cell proliferation assay, clonogenic cell survival assay, and SOD1 activity assay. Results The inhibition of the SOD1 activity enhanced the cisplatin sensitivity in the resistant cells supporting the hypothesis that SOD1 is a key determinant of cisplatin resistance and is an exploitable target to overcome cisplatin drug resistance. Conclusion SOD1 plays an important role in cisplatin resistance and modulation of its activity may overcome this resistance and ultimately lead to improved clinical outcomes.

引用

页码：723 / 730

页数：8

共 43 条

[1]

Auersperg N, 1998, SEMIN ONCOL, V25, P281

[2] In vivo transchelation of copper-64 from TETA-octreotide to superoxide dismutase in rat liver [J].

Bass, LA ;

Wang, M ;

Welch, MJ ;

Anderson, CJ .

BIOCONJUGATE CHEMISTRY, 2000, 11 (04) :527-532

[3] Superoxide dismutase 1 knock-down induces senescence in human fibroblasts [J].

Blander, G ;

de Oliveira, RM ;

Conboy, CM ;

Haigis, M ;

Guarente, L .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (40) :38966-38969

[4]

BRADFORD MM, 1976, ANAL BIOCHEM, V72, P248, DOI 10.1016/0003-2697(76)90527-3

[5]

Chen YM, 2001, GLIA, V33, P343, DOI 10.1002/1098-1136(20010315)33:4<343::AID-GLIA1033>3.0.CO

[6]

2-H

[7] CELL-MEDIATED IMMUNITY TO HUMAN MALIGNANT CELLS - BRIEF REVIEW AND FURTHER STUDIES WITH 2 GYNECOLOGIC TUMORS [J].

DISAIA, PJ ;

RUTLEDGE, FN ;

SMITH, JP ;

SINKOVICS, JG .

AMERICAN JOURNAL OF OBSTETRICS AND GYNECOLOGY, 1972, 114 (07) :979-+

[8]

FEIG DI, 1994, CANCER RES, V54, pS1890

[9] Searching for potential biomarkers of cisplatin resistance in human ovarian cancer using a label-free LC/MS-based protein quantification method [J].

Fitzpatrick, Dawn P. G. ;

You, Jin-Sam ;

Bemis, Kerry G. ;

Wery, Jean-Pierre ;

Ludwig, James R. ;

Wang, Mu .

PROTEOMICS CLINICAL APPLICATIONS, 2007, 1 (03) :246-263

[10] Scavenging activity of indole compounds against cisplatin-induced reactive oxygen species [J].

Fukutomi, Junya ;

Fukuda, Atsushi ;

Fukuda, Satoshi ;

Hara, Masayuki ;

Terada, Atsushi ;

Yoshida, Minoru .

LIFE SCIENCES, 2006, 80 (03) :254-257

← 1 2 3 4 5 →