Sulforaphane attenuates EGFR signaling in NSCLC cells

Journal of Biomedical Science

Tzu-Chien V Wang³  Rui-Mei Huang¹  Yen-Shu Chuang¹  Zhu-Yun Yu¹  Chi-Yuan Chen² 

[1] Research Center for Industry of Human Ecology, Chang Gung University of Science and Technology, Kwei-San 333, Tao-Yuan, Taiwan;Graduate Institute of Health Industry Technology, Chang Gung University of Science and Technology, Kwei-San 333, Tao-Yuan, Taiwan;Department of Molecular and Cellular Biology, College of Medicine, Chang Gung University, Kwei-San 333, Tao-Yuan, Taiwan

关键词: TKI;    HSP90;    Lung cancer;    EGFR;    Sulforaphane;   

Others  :  1213945
DOI  :  10.1186/s12929-015-0139-x

 received in 2015-01-25, accepted in 2015-04-30,  发布年份 2015

【 摘 要 】

Background

EGFR, a receptor tyrosine kinase (RTK), is frequently overexpressed and mutated in non-small cell lung cancer (NSCLC). Tyrosine kinase inhibitors (TKIs) have been widely used in the treatment of many cancers, including NSCLC. However, intrinsic and acquired resistance to TKI remains a common obstacle. One strategy that may help overcome EGFR-TKI resistance is to target EGFR for degradation. As EGFR is a client protein of heat-shock protein 90 (HSP90) and sulforaphane is known to functionally regulate HSP90, we hypothesized that sulforaphane could attenuate EGFR-related signaling and potentially be used to treat NSCLC.

Results

Our study revealed that sulforaphane displayed antitumor activity against NSCLC cells both in vitro and in vivo. The sensitivity of NSCLC cells to sulforaphane appeared to positively correlate with the inhibition of EGFR-related signaling, which was attributed to the increased proteasomal degradation of EGFR. Combined treatment of NSCLC cells with sulforaphane plus another HSP90 inhibitor (17-AAG) enhanced the inhibition of EGFR-related signaling both in vitro and in vivo.

Conclusions

We have shown that sulforaphane is a novel inhibitory modulator of EGFR expression and is effective in inhibiting the tumor growth of EGFR-TKI-resistant NSCLC cells. Our findings suggest that sulforaphane should be further explored for its potential clinical applications against NSCLC.

【 授权许可】

   
2015 Chen et al.; licensee BioMed Central.

【 图 表 】

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