| Objective:1、To investigate effects and mechanisms on proliferation、invasion and apoptosis of the copper complexes with aromatic aldehyde derivatives,which was hereinafter referred to as aromatic aldehyde- copper drug,on breast cancer cell(MCF-7 cell line);2、After the subcutaneous transplantable tumor model of MCF-7cell in nude mice was established,we observed the antineoplastic activity and the toxic and side effort of aromatic aldehyde-copper Drug in contrast with cisplatin.Methords:1、The breast cancer MCF-7 cells were intervened for 24,48 and 72 hours by aromatic aldehyde-copper with different concentrations,and the impact on cell growth was observed,MTT assay was performed to observe the proliferation of MCF-7 treated with aromatic aldehyde-copper;2、The breast cancer MCF-7 cells were intervened for 24 hours by aromatic aldehyde-copper with the concentration of 1.0 and 3.0μmol/L,Tablet Clone Forming experiment was performed to observe the clone formation of MCF-7 treated with aromatic aldehyde-copper;3、The breast cancer MCF-7 cells were intervened for 24 hours by aromatic aldehyde-copper with the concentration of 1.0 and 3.0μmol/L,Transwell Assay was performed to observe the invasion of MCF-7 treated with aromatic aldehyde-copper;4、The breast cancer MCF-7 cells were intervened for 24 and 48 hours by aromatic aldehyde-copper with the concentration of 1.0μmol/L,Annexinv/PI Flow Cytometry was performed to observe the apoptosis of MCF-7 treated with aromatic aldehyde-copper;5、The breast cancer MCF-7 cells were intervened for 24 and 48 hours by aromatic aldehyde-copper with the concentration of 1.0μmol/L,the expression of Protein p53、Bax and Bcl-2 was observed by Western Blotting on MCF-7 treated with aromatic aldehyde-copper;6、The size of subcutaneous MCF-7 transplantable tumor was observed on the nude mice treated with aromatic aldehyde-copper and cicplatin,the growth curves were drawn according to the volume of the tumou,and the tumor growth inhibition rates were calculated.7、The weight、serum creatinine(CREA)、blood urea nitrogen(BUN)、RBC、WBC and PLT were measured on the nude mice treated with aromatic aldehyde-copper and cicplatin.Results:1、Aromatic aldehyde-copper effectively inhibited the proliferation of MCF-7 in a dose-and-time dependent manner, the IC50 was 1.48μmol/L,0.93μmol/L and0.42μmol/L when the cells were treated in 24,48 and 72 hours.2、In contrast with the control,the clone formation of MCF-7 was effectively inhibitted in the groups treated with aromatic aldehyde-copper,the number of clones in group control、1.0μmol/L and 3.0μmol/L was 142.8±11.6,81.2±10.4 and 38.5±8.0.3、In contrast with the control,the invasion ability of MCF-7 was effectively inhibitted in the groups treated with aromatic aldehyde-copper,the cells of migration in group control、1.0μmol/L and 3.0μmol/L was 119.4±15.0,60.5±11.4,32.0±8.1.4 、 Aromatic aldehyde-copper can induce the apoptosis of MCF-7 cells in a time dependent way, which was accompanied with up-regulation of p53 and Bax,while own-regulated of Bcl-2.5、In vivo,Aromatic aldehyde-copper effectively inhibited the growth of subcutaneous MCF-7 tumor in a dose dependent manner.The tumor inhibition rate of aromatic aldehyde-copper(group 0.5mg/kg) was 42.91%,while the rate(group 1mg/kg) was58.84%.6 、 In vivo,the antineoplastic activity of aromatic aldehyde-copper was similar to cisplatin,but the aromatic aldehyde-copper had less effect in renal function and PLT than cisplatin,the difference is statistically significant.Conclusions:1、In vitro,aromatic aldehyde-copper drug may inhibit the proliferation 、 clone formation and aggressivity of MCF-7 cells through inducing cell apoptosis, which should be related to the up-regulation of p53 and Bax,while down-regulated Bcl-2.2、In the animal experiment,the tumor inhibitory effect of aromatic aldehyde-copper was similar to cisplatin,there are little difference in the weight,RBC and WBC of the nude mice,but the aromatic aldehyde-copper had less effect in renal function and PLT than cisplatin. |
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