| Objectives The study was to observe the effects of PPARγactivator rosiglitazone(RSG)and CTGF monoclonal antibody(mAb)on biological behaviour of human gastric cancer cell line BGC-823.We preliminarily explore the mechanism of RSG and CTGFmAb on cancerogenesis as well as their association to provide a new path for clinical treatment.Methods Human gastric cancer cell line BGC-823 were cultured in vitro.The appearance of BGC-823 cells was observed after treated with different concentrations of RSG or CTGFmAb for 24h,48h and 72h.Cells' proliferation was evaluated by MTT colorimetric assay.The invasive and migrative ability of BGC-823 cells were explored by Boyden chamber.The expression levels of CTGFmRNA,COX-2mRNA and MMP-2mRNA were measured by using RT-PCR.The expression of PPARγ,CTGF,COX-2 and MMP-2 were detected by immunohistochemistry.Results(1)PPARγactivator RSG inhibited the proliferation of BGC-823 cells effectively beyond 25μmol/L(P＜0.05 or P＜0.01)whereas there was no dose-effect relationship beyond 50μmol/L.(2)CTGFmAb inhibited the proliferation of BGC-823 cells effectively in 10mg/L～100mg/L range(P＜0.05 or P＜0.01)whereas 0.1mg/L and 1mg/L CTGFmAb failed to inhibite the cells' proliferation.(3)After treated by RSG,BGC-823 cells decreased,volume shrinked,adherent cells decreased,nuclear chromatin condensed at the periphery of caryotheca and suspension cells appeard in culture fluid.BGC-823 cells treated by CTGFmAb decreased,volume shrinked and the appearance of cells changed into fusiform or round.But control group cells usually were round when adhere initially,whereafter cells stretched,turned polygonal,grew prosperously and suspension cells were rarely seen.(4)BGC-823 cells were treated with 50μmol/L RSG for 48h.The number of invasive cells was 74.73±7.35 and the number of migrative cells was 61.23±7.28,there was statistical significance compared with control group(P＜0.05).(5)BGC-823 cells were treated with 10mg/L CTGF mAb for 48h.The number of invasive cells was 79.94±6.08 and the number of migrative cells was 66.74±5.12,there was statistical significance compared with control group(P＜0.05).(6)PRARγproteins were detected in BGC-823 celIs.PRARγproteins increased after BGC-823 cells were treated with RSG,there was statistical significance compared with control group(P＜0.05).(7)CTGF proteins were detected in BGC-823 cells.CTGF proteins decreased after BGC-823 cells were treated with RSG or CTGFmAb,there was statistical significance compared with control group respectively(P＜0.01).(8)COX-2 proteins were detected in BGC-823 cells.COX-2 proteins decreased after BGC-823 cells were treated with RSG or CTGFmAb,there was statistical significance compared with control group respectively(P＜0.01).(9)MMP-2 proteins were detected in BGC-823 cells.MMP-2 proteins decreased after BGC-823 cells were treated with RSG or CTGFmAb,there was statistical significance compared with control group respectively(P＜0.01).(10)CTGFmRNA,COX-2mRNA and MMP-2mRNA were decreased after BGC-823 cells were treated with 50μmol/L RSG,there was statistical significance compared with control group respectively(P＜0.05 or P＜0.01).(11)COX-2mRNA and MMP-2mRNA were decreased after BGC-823 cells treated with 10mg/L CTGFmAb,there was statistical significance compared with control group respectively(P＜0.01).Conclusions(1)PPARγactivator RSG inhibite the proliferation of BGC-823 cells,and the inhibitory action is in a time-and dose-dependent manner at certain range.RSG also decrease the invasive and migrative ability of BGC-823 cells.The effect of RSG on BGC-823 cells may be concerned with activated PPARγmediated- signal pathway.(2)CTGFmAb inhibite the proliferation as well as the invasion and migration of BGC-823 cells.This hint that CTGF may promote the proliferation,invasion and migration of BGC-823 cells. (3)RSG and CTGFmAb alter the appearance of BGC-823 cells.(4)RSG and CTGFmAb decrease the expression of COX-2mRNA and MMP-2mRNA in BGC-823 cells.The effects of RSG and CTGFmAb on BGC-823 cells may be mediated by the down regulation of COX-2 and MMP-2.(5)RSG decrease the expression of CTGFmRNA in BGC-823 cells.These results demonstrate that the inhibitory action of RSG may be mediated by down-regulate CTGF partially.
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