title: Molecular mechanism of indirubin-3'-monoxime and Matrine in the reversal of paclitaxel resistance in NCI-H520/TAX25 cell line.
abstract: BACKGROUND
  Multidrug resistance (MDR) is a main reason for paclitaxel (TAX) treatment failure. Indirubin-3'-monoxime (IRO) and Matrine are traditional Chinese medicines, which may reverse the resistance of tumor cells to some chemotherapy drugs, but the relationship between paclitaxel resistance and Matrine is still unclear. The aim of this study was to explore the potential molecular mechanism of IRO and Matrine in reversal of TAX resistance.
  
  
  METHODS
  In this study, MTT assay was used to measure the non-cytotoxic dosage of IRO and Matrine on NCI-H520/TAX25 cells and determine the reversal extent of TAX resistance under non-toxic doses. In addition, RT-PCR and Western blotting were used to evaluate the mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 cells using semi-quantitative methods.
  
  
  RESULTS
  There was no obvious inhibition on sensitive cell strains and drug-resistant strains, when the final concentration was at lest 4 µmol/L for IRO and 100 µmol/L for Matrine. So 4 µmol/L of IRO and 100 µmol/L of Matrine were considered as the reversal dosage. When 4 µmol/L of IRO or 100 µmol/L of Matrine were used together with TAX, the sensitivity to TAX increased evidently in NCI-H520/TAX2 cells; the reversal rate of IRO and Matrine was about 1.92 (43.56/22.6 nmol/L) and 1.74 (43.56/25.0 nmol/L), respectively. The mRNA expression and the protein level of survivin, Oct-4, and Sox-2 in NCI-H520/TAX25 decreased significantly (P < 0.05) after addition of IRO or Matrine in TAX treatment, compared to that of TAX treatment alone.
  
  
  CONCLUSIONS
  The decrease in both mRNA expression and protein level of survivin, Oct-4, and Sox-2 might be the molecular mechanism, by which IRO and Matrine mediate the reversal of TAX resistance.
authors.affiliation: Department of Medical Oncology, Henan Tumor Hospital, Zhengzhou, Henan 450000, China.
authors.forename: Su-xia
authors.initials: SX
authors.lastname: Luo
authors.forename: Wen-ying
authors.initials: WY
authors.lastname: Deng
authors.forename: Xin-feng
authors.initials: XF
authors.lastname: Wang
authors.forename: Hui-fang
authors.initials: HF
authors.lastname: Lü
authors.forename: Li-li
authors.initials: LL
authors.lastname: Han
authors.forename: Bei-bei
authors.initials: BB
authors.lastname: Chen
authors.forename: Xiao-bing
authors.initials: XB
authors.lastname: Chen
authors.forename: Ning
authors.initials: N
authors.lastname: Li
mesh_terms: D000470:Alkaloids / Q000494:pharmacology*; D015153:Blotting, Western; D045744:Cell Line, Tumor; D019008:Drug Resistance, Neoplasm; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics / Q000378:metabolism; D050814:Octamer Transcription Factor-3 / Q000235:genetics / Q000378:metabolism; D010091:Oximes / Q000494:pharmacology*; D017239:Paclitaxel / Q000494:pharmacology*; D011807:Quinolizines / Q000494:pharmacology*; D055748:SOXB1 Transcription Factors / Q000235:genetics / Q000378:metabolism; D000077022:Survivin; D000093842:Matrines
chemical_list: D000470:Alkaloids; C107489:BIRC5 protein, human; D007211:Indoles; D051034:Inhibitor of Apoptosis Proteins; D050814:Octamer Transcription Factor-3; D010091:Oximes; D011807:Quinolizines; D055748:SOXB1 Transcription Factors; D000077022:Survivin; C474021:indirubin-3'-monoxime; D017239:Paclitaxel; D000093842:Matrines