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Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells.


ABSTRACT:

Purpose

The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non-small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis.

Methods and materials

H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implantation, and microarray analysis. The cisplatin-R cells were treated with human recombinant insulin-like growth factor (IGF) binding protein-3 and siRNA targeting IGF-1 receptor.

Results

Cisplatin-R cells illustrated greater expression of the markers CD133 and aldehyde dehydrogenase, more rapid in vivo tumor growth, more resistance to cisplatin- and etoposide-induced apoptosis, and greater survival after treatment with cisplatin or radiation than the parental H460 cells. Also, cisplatin-R demonstrated decreased expression of insulin-like growth factor binding protein-3 and increased activation of IGF-1 receptor signaling compared with parental H460 cells in the presence of IGF-1. Human recombinant IGF binding protein-3 reversed cisplatin resistance in cisplatin-R cells and targeting of IGF-1 receptor using siRNA resulted in sensitization of cisplatin-R-cells to cisplatin and radiation.

Conclusions

The IGF-1 signaling pathway contributes to cisplatin-R to cisplatin and radiation. Thus, this pathway represents a potential target for improved lung cancer response to treatment.

SUBMITTER: Sun Y 

PROVIDER: S-EPMC3271860 | biostudies-literature | 2012 Mar

REPOSITORIES: biostudies-literature

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Role of insulin-like growth factor-1 signaling pathway in cisplatin-resistant lung cancer cells.

Sun Yunguang Y   Zheng Siyuan S   Torossian Artour A   Speirs Christina K CK   Schleicher Stephen S   Giacalone Nicholas J NJ   Carbone David P DP   Zhao Zhongming Z   Lu Bo B  

International journal of radiation oncology, biology, physics 20111222 3


<h4>Purpose</h4>The development of drug-resistant phenotypes has been a major obstacle to cisplatin use in non-small-cell lung cancer. We aimed to identify some of the molecular mechanisms that underlie cisplatin resistance using microarray expression analysis.<h4>Methods and materials</h4>H460 cells were treated with cisplatin. The differences between cisplatin-resistant lung cancer cells and parental H460 cells were studied using Western blot, MTS, and clonogenic assays, in vivo tumor implanta  ...[more]

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