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Effect of ulinastatin on growth inhibition, apoptosis of breast carcinoma cells is related to a decrease in signal

Hong Wang1, Xin Sun, Feng Gao

  • 1Surgery Department of Breast and Thyroid, Second Affiliated Hospital of Chongqing Medical University, Chongqing 400010, China.

Journal of Experimental & Clinical Cancer Research : CR
|January 6, 2012
PubMed
Abstract

Insights

Ulinastatin (UTI) and Taxotere (TXT) inhibit human breast cancer cell proliferation and xenografted tumor growth. This combination therapy enhances apoptosis and may work by reducing JNK-2 and NF-κB signaling pathways.

Area of Science:

  • Oncology
  • Pharmacology

Background:

  • Breast cancer remains a leading cause of cancer-related deaths globally.
  • Investigating novel therapeutic strategies is crucial for improving patient outcomes.
  • Understanding the molecular mechanisms underlying drug resistance and efficacy is essential.

Purpose of the Study:

  • To evaluate the combined in vitro and in vivo effects of Ulinastatin (UTI) and Taxotere (TXT) on human breast cancer.
  • To assess the impact of UTI and TXT on cancer cell proliferation, apoptosis, and tumor growth.
  • To investigate the modulation of key signaling pathways, including IGF-1R, PDGFA, NGF, JNK-2, and NF-κB.

Main Methods:

  • Cell lines (human primary and MDA-MB-231) were treated with UTI, TXT, or both.
  • MTT assay and flow cytometry were used to measure cell proliferation and apoptosis.
  • RT-PCR and immunohistochemistry were employed to analyze gene and protein expression of target molecules.
  • Xenografted tumor models in nude mice were utilized to assess anti-tumor efficacy.

Main Results:

  • Combined UTI and TXT significantly inhibited breast cancer cell proliferation and xenografted tumor growth compared to individual treatments.
  • Apoptosis was significantly increased in the combination group.
  • Expression of IGF-1R, PDGFA, NGF, JNK-2, and NF-κB at both gene and protein levels was suppressed by UTI and TXT.

Conclusions:

  • Ulinastatin demonstrates anti-proliferative and pro-apoptotic effects on human breast cancer cells.
  • UTI enhances the anti-tumor efficacy of Taxotere, suggesting a synergistic effect.
  • The observed anti-cancer effects are potentially mediated through the downregulation of JNK-2 and NF-κB signaling pathways, impacting downstream targets like IGF-1R, PDGFA, and NGF.

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