title: Astragaloside IV Enhances Cisplatin Chemosensitivity in Non-Small Cell Lung Cancer Cells Through Inhibition of B7-H3.
abstract: BACKGROUND
  Chemoresistance is a major obstacle to successful chemotherapy for human non-small cell lung cancer (NSCLC). Astragaloside IV, the component of Astragalus membranaceus, has been reported to exhibit anti-inflammation, anti-cancer and immunoregulatory properties. In the present study, we investigated the role of astragaloside IV in the chemoresistance to cisplatin in NSCLC cells.
  
  
  METHODS
  We established astragaloside IV-suppressed NSCLC cell lines including A549, HCC827, and NCI-H1299 and evaluated their sensitivity to cisplatin in vitro. In addition, we examined the mRNA and protein levels of B7-H3 in response to cisplatin-based chemotherapy.
  
  
  RESULTS
  We showed that high doses of astragaloside IV (10, 20, 40 ng/ml) inhibited NSCLC cell growth, whereas low concentrations of astragaloside IV (1, 2.5, 5 ng/ml) had no obvious cytotoxicity on cell viability. Moreover, combined treatment with astragaloside IV significantly increased chemosensitivity to cisplatin in NSCLC cells. On the molecular level, astragaloside IV co-treatment significantly inhibited the mRNA and protein levels of B7-H3 in the presence of cisplatin. In addition, ectopic expression of B7-H3 diminished the sensitization role of astragaloside IV in cellular responses to cisplatin in NSCLC cells.
  
  
  CONCLUSIONS
  These results demonstrate that astragaloside IV enhances chemosensitivity to cisplatin via inhibition of B7-H3 and that treatment with astragaloside IV and inhibition of B7-H3 serve as potential therapeutic approach for lung cancer patients.
authors.affiliation: Teaching Hospital of Chengdu University of Traditional Chinese Medicine, Chengdu, China.
authors.forename: Cheng-Shi
authors.initials: CS
authors.lastname: He
authors.forename: Yi-Cheng
authors.initials: YC
authors.lastname: Liu
authors.forename: Zhi-Peng
authors.initials: ZP
authors.lastname: Xu
authors.forename: Peng-Chen
authors.initials: PC
authors.lastname: Dai
authors.forename: Xiao-Wei
authors.initials: XW
authors.lastname: Chen
authors.forename: De-Hai
authors.initials: DH
authors.lastname: Jin
mesh_terms: D017209:Apoptosis / Q000187:drug effects; D060887:B7 Antigens / Q000235:genetics / Q000378:metabolism*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D012503:Saponins / Q000494:pharmacology*; D014315:Triterpenes / Q000494:pharmacology*
chemical_list: D060887:B7 Antigens; C423237:CD276 protein, human; D012503:Saponins; D014315:Triterpenes; C052064:astragaloside A; D002945:Cisplatin