Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line.

Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Research Abstract Details 

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Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Abstract Text:

Marzia B Gariboldi,Raffaella Ravizza,Roberta Molteni,Domenico Osella,Elisabetta Gabano,Elena Monti,Marzia B Gariboldi,Raffaella Ravizza,Roberta Molteni,Domenico Osella,Elisabetta Gabano,Elena Monti,

Metastatic breast cancer is an incurable disease, often characterized by poor response to standard chemotherapy, which is mainly based on anthracyclines and taxanes. Thus, increasing tumor cell sensitivity to these agents is an attractive goal towards improving the clinical management of this disease. The present study investigates the effects of signal transducer and activator of transcription 3 (Stat3) inhibition on the response of the highly metastatic MDA-MB-231 human breast adenocarcinoma cell line to doxorubicin (DOX). Stat3 is a transcription factor often constitutively activated in breast tumors and cancer cell lines, and is thought to contribute to malignant transformation and progression by transactivation of a host of target genes involved in cell proliferation and survival, angiogenesis and invasiveness. Our results indicate that (a) untreated MDA-MB-231 cells express higher baseline levels of (activated) pTyr(705)Stat3, that are further upregulated following exposure to DOX, than the non-metastatic MCF-7 cell line; (b) inhibiting the Stat3 signaling pathway, by exposure to the tyrphostin AG490 (an inhibitor of the upstream activating Janus kinases), by transfection with a dominant-negative form of Stat3 or by treatment with satraplatin (a tetravalent platinum derivative that inhibits Stat3 activation), increases breast cancer cell response to the proapoptotic effect of DOX (to different extents). In addition, the latter two approaches have been shown to interfere with expression of one or more antiapoptotic proteins. Overall, these observations suggest that suppression of Stat3 signaling may provide a potential therapeutic approach to overcoming DOX resistance in metastatic breast cancer cells.

Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Publishing Authors By Initials

MB Gariboldi,R Ravizza,R Molteni,D Osella,E Gabano,E Monti,MB Gariboldi,R Ravizza,R Molteni,D Osella,E Gabano,E Monti,

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Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Cancer letters

VOLUME: 258

Page Numbers: 181-8

Journal Abbreviation: Cancer Lett.

ISSN: 0304-3835

DAY: 24

MONTH: 10

YEAR: 2007

Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line. Information

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LANGUAGE: eng

NlmUniqueID: 7600053

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Grant and Affiliation Information for Inhibition of Stat3 increases doxorubicin sensitivity in a human metastatic breast cancer cell line.

AFFILIATION: Department of Structural and Functional Biology, Section of Pharmacology, University of Insubria, Via A. da Giussano 12, 21052 Busto Arsizio, Italy.

Country: Ireland

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MEDLINETA: Cancer Lett

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