title: Synergistic anticancer effects of andrographolide and paclitaxel against A549 NSCLC cells.
abstract: BACKGROUND
  Paclitaxel (PTX) is widely used in chemotherapy for cancer treatment; however, it has some serious side effects. Andrographolide (Andro) is a potential cancer therapeutic agent isolated from Andrographis paniculata (Burm. f.) Nees (Acanthaceae).
  
  
  OBJECTIVE
  The objective of this study is to evaluate the effects of PTX combined with Andro against A549 cells.
  
  
  METHODS
  The effects of 24-48 h treatment with 0.48-60.75 nM PTX and 5.10-328.0 μM Andro on cellular proliferation, apoptosis, cell cycle and intracellular reactive oxygen species (ROS) were determined by sulphorhodamine B assay, Annexin V-FITC/PI apoptosis detection, PI staining and ROS assay, respectively. Synergy was determined using combination index. The antitumour efficacy of 20 mg/kg PTX with 100 mg/kg Andro was studied in a xenograft murine model.
  
  
  RESULTS
  IC50value of the PTX combined with Andro against A549 cells was 0.5-7.4 nM, which was significantly lower than that of PTX (15.9 nM). PTX with 10 μM Andro caused (1.22-1.27)-fold apoptosis and 1.7-fold ROS accumulation compared with PTX alone. N-Acetylcysteine, a ROS scavenger, blocked this synergy in vitro. In contrast, G2/M phase cell cycle arrest resulting from PTX was not potentiated by Andro. Moreover, PTX in combination with Andro inhibited the growth of A549 transplanted tumours by 98%.
  
  
  CONCLUSIONS
  The results indicate that the combination of PTX and Andro exert significant synergistic anticancer effect on A549 cells in vitro and in vivo. The synergy may be the result of the accumulation of ROS. The combination of Andro and PTX represents a potential strategy for the treatment of A549 cells.
authors.affiliation: a Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering , East China University of Science and Technology , Shanghai , China.
authors.forename: Huihui
authors.initials: H
authors.lastname: Yuan
authors.affiliation: a Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering , East China University of Science and Technology , Shanghai , China.
authors.forename: Bo
authors.initials: B
authors.lastname: Sun
authors.affiliation: b Department of Pharmaceutics, School of Pharmacy , East China University of Science and Technology , Shanghai , China.
authors.forename: Feng
authors.initials: F
authors.lastname: Gao
authors.affiliation: a Shanghai Key Laboratory of Functional Materials Chemistry, School of Chemistry and Molecular Engineering , East China University of Science and Technology , Shanghai , China.|c State Key Laboratory of Bioreactor Engineering, School of Biotechnology , East China University of Science and Technology , Shanghai , China.
authors.forename: Minbo
authors.initials: M
authors.lastname: Lan
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002289:Carcinoma, Non-Small-Cell Lung / Q000188:drug therapy* / Q000473:pathology; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004224:Diterpenes / Q000494:pharmacology*; D004357:Drug Synergism; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D017239:Paclitaxel / Q000494:pharmacology*; D017382:Reactive Oxygen Species / Q000378:metabolism
chemical_list: D004224:Diterpenes; D017382:Reactive Oxygen Species; C030419:andrographolide; D017239:Paclitaxel
keywords: Antiproliferation; ROS; antitumour; apoptosis; cell cycle