title: Cryptotanshinone Reverses Cisplatin Resistance of Human Lung Carcinoma A549 Cells through Down-Regulating Nrf2 Pathway.
abstract: OBJECTIVE
  To explore whether Nrf2 was associated with drug-resistance in cisplatin resistant A549 (A549/DDP) cells, and if cryptotanshinone (CTS), one of the bioactive compounds isolated from the roots of Salvia miltiorrhiza Bunge (Danshen), could enhance the sensitivity in A549/DDP cells towards cisplatin.
  
  
  METHODS
  A549 and A549/DDP cells were subjected to various treatments, and then Sulforhodamine B (SRB) assay, flow cytometry analysis and western immunoblotting analysis were applied to determine IC50, apoptotic status and expressions of Nrf2 and its downstream genes.
  
  
  RESULTS
  The endogenous expression levels of Nrf2 as well as its target genes including GCLC, GCLM, HO-1, NQO1 and MRP1 were much higher in A549/DDP cells than those of A549 cells and the susceptibility of A549/DDP cells to cisplatin was partially restored by silencing Nrf2. The combination of CTS and cisplatin led to cell death and apoptosis through sensitizing A549/DDP cells towards cisplatin compared with cisplatin mono-treatment, however, this reversal role could be abolished by Nrf2 knockdown. Specifically, CTS obviously diminished Nrf2 expression, thus contributing to the decrease of Nrf2-target genes expression levels. Meanwhile, we also discovered that CTS triggered several other signals involving in chemoresistance such as MAPKs, Akt and STAT3 pathway.
  
  
  CONCLUSIONS
  Our data indicated CTS may be developed as a potential sensitizer cooperating with anticancer drugs to combat chemoresistant carcinoma through the inhibition of the Nrf2 pathway.
authors.affiliation: School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xia
authors.forename: Xupeng
authors.initials: X
authors.lastname: Bai
authors.forename: Xiangyu
authors.initials: X
authors.lastname: Hou
authors.forename: Xiaoli
authors.initials: X
authors.lastname: Gou
authors.forename: Yongtao
authors.initials: Y
authors.lastname: Wang
authors.forename: Hang
authors.initials: H
authors.lastname: Zeng
authors.forename: Min
authors.initials: M
authors.lastname: Huang
authors.forename: Jing
authors.initials: J
authors.lastname: Jin
mesh_terms: D017209:Apoptosis; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology; D015536:Down-Regulation; D019008:Drug Resistance, Neoplasm / Q000187:drug effects*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy / Q000378:metabolism*; D051267:NF-E2-Related Factor 2 / Q000378:metabolism*; D010616:Phenanthrenes / Q000494:pharmacology*; D015398:Signal Transduction / Q000187:drug effects*
chemical_list: D051267:NF-E2-Related Factor 2; C495635:NFE2L2 protein, human; D010616:Phenanthrenes; C037886:cryptotanshinone; D002945:Cisplatin