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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.

Wang H, Sun X, Gao F, Zhong B, Zhang YH, Sun Z - J. Exp. Clin. Cancer Res. (2012)

Bottom Line: The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group.Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.This mechanism might be related to decreasing signal transduction of JNk-2 and NF-κB, and then expression of IGF-1R, PDGFA, NGF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgery Department of Breast and Thyroid, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

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.

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Effect of UTI and TXT on the protein expression of NGF in MDA-MB-231 xenografted tumor tissue of nude mice.
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Figure 11: Effect of UTI and TXT on the protein expression of NGF in MDA-MB-231 xenografted tumor tissue of nude mice.

Mentions: Immunohistochemistry showed that UTI, TXT, and UTI+TXT significantly inhibited the protein expression of PDGFA, NGF, and IGF-1R compared with the control group (P < 0.05). The inhibitory effect of UTI+TXT was strongest. The expression of ki-67, JNk-2, and NF-κB was reduced in the UTI, TXT, and UTI+TXT groups; however, the protein expression of caspase-3 increased significantly, and this effect was strongest for UTI+TXT (P < 0.05;Figure 9, 10, 11).


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.

Wang H, Sun X, Gao F, Zhong B, Zhang YH, Sun Z - J. Exp. Clin. Cancer Res. (2012)

Effect of UTI and TXT on the protein expression of NGF in MDA-MB-231 xenografted tumor tissue of nude mice.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3275539&req=5

Figure 11: Effect of UTI and TXT on the protein expression of NGF in MDA-MB-231 xenografted tumor tissue of nude mice.
Mentions: Immunohistochemistry showed that UTI, TXT, and UTI+TXT significantly inhibited the protein expression of PDGFA, NGF, and IGF-1R compared with the control group (P < 0.05). The inhibitory effect of UTI+TXT was strongest. The expression of ki-67, JNk-2, and NF-κB was reduced in the UTI, TXT, and UTI+TXT groups; however, the protein expression of caspase-3 increased significantly, and this effect was strongest for UTI+TXT (P < 0.05;Figure 9, 10, 11).

Bottom Line: The cell lines cultured were divided into four groups: 1) control group, 2) UTI group, 3) TXT group, and 4) UTI+TXT group.Immunohistochemistry staining (SP) was used to detect the expression of IGF-1R, PDGFA, NGF, ki-67, caspase-3, JNk-2, and NF-κB.This mechanism might be related to decreasing signal transduction of JNk-2 and NF-κB, and then expression of IGF-1R, PDGFA, NGF.

View Article: PubMed Central - HTML - PubMed

Affiliation: Surgery Department of Breast and Thyroid, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

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.

Show MeSH
Related in: MedlinePlus