Article

Akt is the downstream target of GRP78 in mediating cisplatin resistance in ER stress-tolerant human lung cancer cells.

Thoracic Surgery Department, West China Hospital, Sichuan University School of Medicine, Chengdu Sichuan Province 610041, China.
Lung cancer (Amsterdam, Netherlands) (impact factor: 3.14). 03/2011; 71(3):291-7. DOI:10.1016/j.lungcan.2010.06.004 pp.291-7
Source: PubMed

ABSTRACT Cisplatin [cis-diaminodichloroplatinum (II) (CDDP)] is the cornerstone of lung cancer chemotherapy. However, its efficacy is limited due to the development of drug resistance in cancer cells. This study was designed to uncover the mechanisms under CDDP resistance in lung cancer cells involving endoplasmic reticulum (ER) stress tolerance-induced and GRP78-dependant Akt activation. In this study we established ER stress-tolerant (ERST) human lung cancer lines H460et and A549et. We found that the ERST Lung cancer cells are resistant to CDDP treatment. We further showed that, compared to the parental cell lines, H460et and A549et show significantly increased GRP78 and phospho(p)-Akt levels. And phosphorylation of Akt, which can be regulated by GRP78, is essential to the ERST-associated CDDP resistance. Our findings identify a new mechanism of regulating Akt activity and a new mechanism through which CDDP resistance is formed in lung cancer cells.

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Keywords

cancer cells
 
CDDP resistance
 
CDDP treatment
 
Cisplatin [cis-diaminodichloroplatinum
 
drug resistance
 
endoplasmic reticulum
 
ERST Lung cancer cells
 
ERST-associated CDDP resistance
 
GRP78-dependant Akt activation
 
lung cancer cells
 
lung cancer chemotherapy
 
new mechanism
 
parental cell lines
 
phospho(p)-Akt levels
 
regulating Akt activity
 

Yidan Lin