Downregulation of insulin-like growth factorbinding protein 7 in cisplatin-resistant non-small cell lung cancer

Jun Okamura, Yiping Huang, David Moon, Mariana Brait, Xiaofei Chang, Myoung Sook Kim

Research output: Contribution to journalArticlepeer-review

Abstract

Cisplatin is an effective anticancer drug used to treat many types of cancer, including non-small cell lung carcinoma (NSCLCs), but development of resistance is the primary impediment in cancer treatment. Insulin-like growth factorbinding protein 7 (IGFBP7) is a secreted tumor suppressor that is inactivated in human lung cancer. IGFBP7 is known to alter sensitivity to interferon-based anticancer therapy, and here, we examined loss of IGFBP7 as a potential contributor to chemo-resistance to cisplatin. The transcriptional level of IGFBP7 was decreased in cisplatin-resistant human cancer cell lines and NSCLC xenografts. IGFBP7 knock-down increased cellular resistance to cisplatin and increased the level of mitogen-activated protein kinase phosphatases (MKP) 3 levels. The expression of MKP3 increased in a cisplatin-resistant NSCLC cell line and lung xenografts. MKP3 knock-down increased IGFBP7 level, indicating that MKP3 regulates IGFBP7. These findings suggest a novel molecular mechanism responsible for the tumor suppressive function of IGFBP7 in cisplatin-resistant human lung cancer and could lead to the development of IGFBP7 as a cisplatin-sensitizing agent.

Original languageEnglish (US)
Pages (from-to)148-155
Number of pages8
JournalCancer Biology and Therapy
Volume13
Issue number3
DOIs
StatePublished - Feb 1 2012

Keywords

  • Cisplatin resistance
  • Erk
  • Human xenografts
  • IGFBP7
  • MKP3
  • NSCLC
  • Stat3

ASJC Scopus subject areas

  • Molecular Medicine
  • Oncology
  • Pharmacology
  • Cancer Research

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