Effect of ulinastatin on growth inhibition, apoptosis of breast carcinoma cells is related to a decrease in signal conduction of JNk-2 and NF-κB.

Abstract

OBJECTIVE:

This study aims to investigate the in vitro effects of Ulinastatin (UTI) and Taxotere (TXT) on cell proliferation; cell apoptosis; xenografted tumor growth; and expression of insulin-like growth factor receptor 1 (IGF-1R), platelet-derived growth factor A (PDGFA), nerve growth factor (NGF), c-Jun N-terminal kinase 2 (JNk-2), and NF-κB in a human primary breast cancer cells and breast cancer cell line MDA-MB-231.

METHODS:

The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group. The method of MTT essay, flow cytometry, and RT-PCR were used to detect cell proliferation, cell apoptosis, and expression of IGF-1R, PDGFA, NGF, NF-κB, JNk-2, respectively. The growth of xenografted tumor in nude mice was used to calculate the anti-tumor rate. Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.

RESULTS:

Proliferation of human breast cancer cells and MDA-MB-231 cell lines, and growth rate of xenografted tumor decreased in order of UTI+TXT > TXT > UTI > control, apoptosis increased in the order control < UTI < TXT < UTI+TXT. The gene expression and protein expression of IGF-1R, PDGFA, NGF, NF-κB and JNk-2 in breast cancer cells was inhibited by UTI and TXT.

CONCLUSIONS:

UTI 1) inhibits the proliferation of human breast cancer cells and the growth of xenografted tumors, 2) induces cancer cell apoptosis, and 3) enhances the anti-tumor effect of TXT. This mechanism might be related to decreasing signal transduction of JNk-2 and NF-κB, and then expression of IGF-1R, PDGFA, NGF.

• Authors: Hong Wang, Xin Sun, Feng Gao, Biao Zhong, Yong-Hua Zhang, Zhijun Sun
• Journal: Journal of experimental & clinical cancer research : CR (J Exp Clin Cancer Res) Vol. 31 Pg. 2 (Jan 05 2012) ISSN: 1756-9966 [Electronic] England
• PMID: 22217202 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Glycoproteins
• NF-kappa B
• Taxoids
• Docetaxel
• Mitogen-Activated Protein Kinase 9
• urinastatin

Topics

• Animals
• Apoptosis (drug effects)
• Breast Neoplasms (genetics, metabolism, pathology)
• Cell Line, Tumor
• Cell Proliferation (drug effects)
• Docetaxel
• Female
• Gene Expression Regulation, Neoplastic (drug effects)
• Glycoproteins (administration & dosage)
• Humans
• Mice
• Mice, Nude
• Mitogen-Activated Protein Kinase 9 (genetics, metabolism)
• NF-kappa B (genetics, metabolism)
• Signal Transduction (drug effects)
• Taxoids (administration & dosage)
• Transplantation, Heterologous