[Nrf2 down-regulated cell line H460-N5 with Keap1 over-expression increased sensitivity to anti-cancer drugs].
Zhejiang Da Xue Xue Bao Yi Xue Ban
; 39(1): 6-10, 2010 01.
Article
in Zh
| MEDLINE
| ID: mdl-20175229
ABSTRACT
OBJECTIVE:
To maked a Nrf2 down-regulated cell line by over-expressing Keap1 in H460 cells to study the role of Nrf2 in drug resistance.METHODS:
Transfecting H460 cells with mKeap1-pEGFP and screenig for Keap1 expressing clones by Western blotting with antibodies against Nrf2, HO-1, NQO1 and AKR1C. The cell line with Keap1 over-expression was further confirmed by real-time PCR. The cytotoxicity of H460-N5 to anti-cancer drugs was evaluated by MTS assay.RESULT:
MTS assay results showed the enhanced cytotoxicity of anticancer drugs (Oxaliplatin, Doxorubicin and Etopside) to the H460 cell line with keap1 overexpression compared to the control cell line. In H460-N0 cells, the IC(50) values of Oxaliplation and Etopside were 93 micromol/L and 100 micromol/L respectively whereas the IC(50) values of the two drugs were 42 micromol/L and 30 micromol/L correspondingly in H460-N5 cells. A Nrf2 down-regulated cell line H460-N5 and a control cell line with GFP over-expression have been identified.Down-regulation of Nrf2 enhanced the cytotoxicity of Oxaliplatin, Doxorubicin and Etopside. The IC(50) value of Doxorubicin to H460-N0 cell was above 3 mg/L, but that to H460-N5 cell was about 2 mg/L.CONCLUSION:
A Nrf2 down-regulated cell line H460-N5 and a control cell line with GFP over-expression have been identified. Down-regulation of Nrf2 enhanced the cytotoxicity of Oxaliplatin, Doxorubicin and Etopside.
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Collection:
01-internacional
Database:
MEDLINE
Main subject:
Signal Transduction
/
Drug Resistance, Neoplasm
/
Intracellular Signaling Peptides and Proteins
/
NF-E2-Related Factor 2
/
Antineoplastic Agents
Type of study:
Diagnostic_studies
/
Prognostic_studies
Limits:
Humans
Language:
Zh
Journal:
Zhejiang Da Xue Xue Bao Yi Xue Ban
Journal subject:
MEDICINA
Year:
2010
Type:
Article
Affiliation country:
China