title: [Somatostatin enhanced anti-tumor effect of doxorubicin on gallbladder cancer cells through the regulation of intracellular drug concentration].
abstract: OBJECTIVE
  To investigate the possible mechanisms by which Somatostatin (SST) enhances the anti-tumor effect of doxorubicin (DOX) on gallbladder cancer cells.
  
  
  METHODS
  GBC-SD cells were grouped into 4 groups: SST-treated group, DOX-treated group, SST+DOX co-treated group and control group. The concentrations of SST and DOX were 75 µg/ml and 5 µg/ml based on our previous studies. In control group, cells were cultivated with phosphate buffered saline (PBS). In experimental groups, cells were cultivated with medium and the corresponding drugs. After drug treatment, cell viability was examined by MTT assay at 6, 12, 24 and 36 h respectively. Meanwhile, intracellular concentrations of doxorubicin in each group was determined by microspectrofluorimetry; Real-time polymerase chain reaction (RT-PCR) was used to determine the expressions of MDR1 mRNA in the cells at different time points and the expressions of P-gp protein, a product of MDR1 mRNA, were determined by Western blot analysis.
  
  
  RESULTS
  SST did not exhibit significant inhibitory effect on the proliferation of GBC-SD cells as compared to that of control group (P>0.05). SST+DOX co-treatment group and DOX showed significantly inhibitory effect on the growth of GBC-SD cells at Hour 12 post-treatment. However no statistical difference was found between SST+DOX and DOX groups. Interestingly, at Hour 24 post-treatment, SST+DOX group showed more robust inhibitory effect on GBC-SD cells as compared to DOX alone group. Moreover, SST could significantly down-regulate the expressions of MDR1 mRNA and P-gp protein. SST could increase intracellular DOX concentration. And the difference of intracellular DOX concentration between SST+DOX group and DOX group at Hour 24 was statistically significant.
  
  
  CONCLUSIONS
  In our experiment, SST decreases the expression of MDR1 mRNA and P-gp protein so as to reduce the efflux of DOX and elevate DOX concentrations in GBC-SD cells. This eventually leads to enhanced cytotoxic effects of DOX on GBC-SD cells.
authors.affiliation: Department of General Surgery, Xinhua Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200092, China.
authors.forename: Wei
authors.initials: W
authors.lastname: Gong
authors.forename: Yi-yu
authors.initials: YY
authors.lastname: Qin
authors.forename: Song-gang
authors.initials: SG
authors.lastname: Li
authors.forename: Zhi-wei
authors.initials: ZW
authors.lastname: Quan
authors.forename: Ji-yu
authors.initials: JY
authors.lastname: Li
authors.forename: Peng-yuan
authors.initials: PY
authors.lastname: Zhuang
authors.forename: Zi-wei
authors.initials: ZW
authors.lastname: Wan
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004317:Doxorubicin / Q000494:pharmacology* / Q000627:therapeutic use; D004357:Drug Synergism; D005706:Gallbladder Neoplasms / Q000188:drug therapy; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D013004:Somatostatin / Q000494:pharmacology*
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D013004:Somatostatin; D004317:Doxorubicin