title: Synergistic anticancer effects of polyphyllin I and evodiamine on freshly-removed human gastric tumors.
abstract: OBJECTIVE
  The present study was designed to examine the anticancer effect of Traditional Chinese Medicine of polyphyllin I (PPI) and evodiamine (EVO) on freshly-removed gastric tumor tissues.
  
  
  METHODS
  Sixty freshly-removed gastric tumor tissues were collected. Their sensitivity to PPI, EVO, platinum (Pt), 5-FU, irinotecan (CPT-11) were determined by histoculture drug response assay (HDRA). Those samples were also formalin-fixed and paraffin-embedded, which were used to examine the mRNA expression levels of aprataxin(APTX), excision repair cross-complementing 1(ERCC1), thymidylate synthase(TS) and topoisomerase I(TOPO1) by quantitative RT-PCR. The association of the gene expression levels and in vitro sensitivity were analyzed.
  
  
  RESULTS
  PPI, EVO, Pt, 5-FU and CPT-11 had anticancer effects on the freshly-removed gastric tumor tissues with average inhibition rates of 20.64%±14.25% for PPI, 21.14%±13.43% for EVO, 50.57%±22.37% for Pt, 53.54%±22.03% for 5-FU, and 39.33%±24.79% for CPT-11, respectively. Combination of PPI and Pt, EVO and Pt, EVO and 5-FU had higher inhibition rates than any single drug of them (P<0.001, P = 0.028, P = 0.017, respectively). The mRNA expression levels of ERCC1 were correlated with Pt sensitivity (rho = -0.645, P<0.001); the mRNA expression levels of TS were correlated with 5-FU sensitivity (rho = -0.803, P<0.001). There were also weak but significant correlations between APTX mRNA expression levels and CPT-11 sensitivity (rho = -0.376, P = 0.017) or EVO sensitivity (rho = -0.322, P = 0.036). ERCC1 mRNA expression levels was markedly suppressed by the presentation of PPI (P = 0.001) and slightly suppressed by the presentation of EVO (P = 0.04); whereas, TS mRNA expression levels was markedly decreased by the presentation of EVO (P = 0.017) and slightly decreased by the presentation of PPI (P = 0.047).
  
  
  CONCLUSIONS
  PPI and EVO both could inhibit the activity of freshly-removed gastric tumor, and they could enhance the anticancer effect of Pt and 5-FU by reducing the mRNA expression levels of ERCC1 and TS.
authors.affiliation: The Comprehensive Cancer Centre, Drum Tower Clinical Medical College of Nanjing University of Chinese Medicine, Nanjing, Jiangsu, China.
authors.forename: Guofeng
authors.initials: G
authors.lastname: Yue
authors.forename: Jia
authors.initials: J
authors.lastname: Wei
authors.forename: Xiaoping
authors.initials: X
authors.lastname: Qian
authors.forename: Lixia
authors.initials: L
authors.lastname: Yu
authors.forename: Zhengyun
authors.initials: Z
authors.lastname: Zou
authors.forename: Wenxian
authors.initials: W
authors.lastname: Guan
authors.forename: Hao
authors.initials: H
authors.lastname: Wang
authors.forename: Jie
authors.initials: J
authors.lastname: Shen
authors.forename: Baorui
authors.initials: B
authors.lastname: Liu
mesh_terms: D000971:Antineoplastic Combined Chemotherapy Protocols / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology / Q000627:therapeutic use; D016001:Confidence Intervals; D004144:Diosgenin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D019008:Drug Resistance, Neoplasm / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D004357:Drug Synergism; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology / Q000627:therapeutic use; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D052138:Genes, Neoplasm / Q000235:genetics; D006801:Humans; D000077146:Irinotecan; D008297:Male; D008875:Middle Aged; D009363:Neoplasm Proteins / Q000235:genetics / Q000378:metabolism; D010984:Platinum / Q000494:pharmacology / Q000627:therapeutic use; D011799:Quinazolines / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000473:pathology
chemical_list: D009363:Neoplasm Proteins; D011799:Quinazolines; D012333:RNA, Messenger; C556217:polyphyllin I; D010984:Platinum; D000077146:Irinotecan; C049639:evodiamine; D004144:Diosgenin; D005472:Fluorouracil; D002166:Camptothecin