SV40 T/t-common polypeptide enhances the sensitivity of HER2-overexpressing human cancer cells to anticancer drugs cisplatin and doxorubicin

Cancer Lett. 2012 Nov 1;324(1):48-57. doi: 10.1016/j.canlet.2012.04.019. Epub 2012 Apr 27.

Abstract

HER2-overexpressing cancer cells are resistant to cisplatin (CDDP) and doxorubicin (DXR). Here we report that SV40 T/t-common polypeptide could specifically sensitize HER2-overexpressing cancer cells to CDDP and DXR and specifically enhance CDDP- or DXR-induced apoptosis in these cells. This activity of T/t-common may be attributed to its ability to inhibit Bcl-2 and Bcl-XL and to suppress ERK activity in CDDP- or DXR-treated HER2-overexpressing cancer cells. T/t-common could enhance the antitumor activity of DXR on HER2-overexpressing ovarian tumor in NOD/SCID mice, suggesting that combination therapy using T/t-common and chemotherapeutic agents may provide a new approach for treating HER2-overexpressing cancers.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Polyomavirus Transforming / genetics
  • Antigens, Polyomavirus Transforming / metabolism*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects
  • Cisplatin / pharmacology*
  • Doxorubicin / pharmacology*
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Mice
  • Mice, SCID
  • Ovarian Neoplasms / drug therapy
  • Ovarian Neoplasms / genetics
  • Ovarian Neoplasms / metabolism
  • Proto-Oncogene Proteins c-bcl-2 / genetics
  • Proto-Oncogene Proteins c-bcl-2 / metabolism
  • Receptor, ErbB-2 / genetics
  • Receptor, ErbB-2 / metabolism*
  • Tumor Cells, Cultured
  • Xenograft Model Antitumor Assays
  • bcl-X Protein / genetics
  • bcl-X Protein / metabolism

Substances

  • Antigens, Polyomavirus Transforming
  • Antineoplastic Agents
  • BCL2L1 protein, human
  • Proto-Oncogene Proteins c-bcl-2
  • bcl-X Protein
  • Doxorubicin
  • ERBB2 protein, human
  • Receptor, ErbB-2
  • Cisplatin