title: Synergistic anti-proliferative effects of gambogic acid with docetaxel in gastrointestinal cancer cell lines.
abstract: BACKGROUND
  Gambogic acid has a marked anti-tumor effect for gastric and colorectal cancers in vitro and in vivo. However, recent investigations on gambogic acid have focused mainly on mono-drug therapy, and its potential role in cancer therapy has not been comprehensively illustrated. This study aimed to assess the interaction between gambogic acid and docetaxel on human gastrointestinal cancer cells and to investigate the mechanism of gambogic acid plus docetaxel treatment-induced apoptotic cell death.
  
  
  METHODS
  MTT assay was used to determine IC(50) values in BGC-823, MKN-28, LOVO and SW-116 cells after gambogic acid and docetaxel administration. Median effect analysis was applied for determination of synergism and antagonism. Synergistic interaction between gambogic acid and docetaxel was evaluated using the combination index (CI) method. Furthermore, cellular apoptosis was analyzed by Annexin-V and propidium iodide (PI) double staining. Additionally, mRNA expression of drug-associated genes, i.e., β-tublin III and tau, and the apoptosis-related gene survivin, were measured by quantitative reverse transcription polymerase chain reaction (qRT-PCR).
  
  
  RESULTS
  Gambogic acid provided a synergistic effect on the cytotoxicity induced by docetaxel in all four cell lines. The combined application of gambogic acid and docetaxel enhanced apoptosis in gastrointestinal cancer cells. Moreover, gambogic acid markedly decreased the mRNA expression of docetaxel-related genes, including β-tubulin III, tau and survivin, in BGC-823 cells.
  
  
  CONCLUSIONS
  Gambogic acid plus docetaxel produced a synergistic anti-tumor effect in gastrointestinal cancer cells, suggesting that the drug combination may offer a novel treatment option for patients with gastric and colorectal cancers.
authors.affiliation: The Comprehensive Cancer Center of Drum Tower Hospital, Medical School of Nanjing University, China.
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Zou
authors.forename: Li
authors.initials: L
authors.lastname: Xie
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.forename: Junhao
authors.initials: J
authors.lastname: Chen
authors.forename: Tingting
authors.initials: T
authors.lastname: Wang
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077143:Docetaxel; D004357:Drug Synergism; D041743:Herb-Drug Interactions; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D020128:Inhibitory Concentration 50; D008517:Phytotherapy; D010936:Plant Extracts / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D014404:Tubulin / Q000235:genetics / Q000378:metabolism; D044004:Xanthones / Q000008:administration & dosage / Q000494:pharmacology / Q000627:therapeutic use*; D016875:tau Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D051034:Inhibitor of Apoptosis Proteins; D010936:Plant Extracts; D012333:RNA, Messenger; D000077022:Survivin; C498585:TUBB3 protein, human; D043823:Taxoids; D014404:Tubulin; D044004:Xanthones; D016875:tau Proteins; D000077143:Docetaxel; C052659:gambogic acid