| 【Objective and significance】PPO is a new cancer genes associated with the proliferation and phosphorylation oftumor cell, which is highly expressed in a variety of adenocacinoma. The finding of PPOprovide a new idea and research direction for the diagnosis and treatment of prostatecancer. The specificity of angiogenic factor VEGF is strong, its combination withVEGFR can cause a variety of signal transduction which will stimulate the formation oftumor angiogenesis and lymphatic vessels. Also it provide blood support for theoccurrence, development and metastasis of cancer cell. As2O3can inhibit the activity oftumor cell VEGF and PPO effectively and induce the apoptosis of tumor cell, which alsocan inhibit the proliferation of cancer cell. In this experiment, the effects of As2O3, VCand the combination of the two on the growth, proliferation, cell cycle and apoptosis ofhuman lung adenocarcinoma A549cells in vitro was observed. The mechanism of thetwo drugs on human lung adenocarcinoma A549cell was studied initially, which providenew methods and ideas for the diagnosis and treatment of lung cancer.【Method】Human lung adenocarcinoma cell A549was subcultured in incubator with saturatedhumidity temperature37℃,5%CO2. Logarithmic phase cells were tested. Intervene thecell with different drugs and different concentration according to the test group. Theabsorbance of different groups were determined by four methyl thiazolyl tetrazolium(MTT) method and the growth inhibition rate was also calculated. The effects of drugs oncell morphology was observed under a microscope. Cell cycle and apoptosis rate were detected with flow cytometry. The expression of PPO and VEGF after the treatment ofAs2O3and VC on lung adenocarcinoma A549cells was detected by immunohistochem-ical.【Result】1. As2O3can inhibit the proliferation of A549cells, which has dependence on timeand concentration. When the concentration of As2O3was1μmol/L, the comparison ofinhibition ratio of A549cell treated for48hours and72hours indicates that P﹤0.05.There is significant difference between the remaining group and control group, P﹤0.01.VC has a certain inhibitory action on the proliferation of lung adenocarcinoma A549cells.The inhibition action on the growth of A549cell is not significant under smalldose(100-400μg/ml). There is no dependence on time (P＞0.05)and obvious differencewhen the concentration of VC is10μg/ml. When the concentration of VC was800and1600μg/ml, there is a significant growth inhibitory effect on A549cell and dependenceon time and concentration. The combination of VC(400μg/ml) and As2O3with differentconcentration has significant inhibitory effect on proliferation of target cells, and there istime and dose effect relationship. The comparison among groups was statisticallysignificant, P﹤0.01. The inhibition effect of combined drugs treatment of cells wasobviously higher than that of single drug.2. Human lung adenocarcinoma cells were detained by2μ mol/L As2O3at G2/Mphase. After treated by400μmol/L VC for48hours, the target cells appeared G0/G1block. There is significant difference compared with the control group, P﹤0.01. Theproportion of apoptosis-inducing introduced by combined group is larger than that ofAs2O3group and VC group. Cells at G2/M、G0/G1phase treated by combined drugswere more than the control group. After treated by400μ mol/L VC for48hours, theapoptosis rate of target cells increased with low margin compared with the control group,P＜0.05. There is no significant difference between the proportion at G2/M phase ofcells treated by combined group and As2O3group.3. After A549cells was treated by As2O3(2μmol/L) for48hours, PPO gene andVEFG protein were significantly decreased(P＜0.0083). After A549cells was treated by VC(400μ mol/L) for48hours, VEFG protein were significantly decreased(P＜0.0083).however, there is almost no difference between PPO gene and the control group, P＞0.0083. After the target cells was treated by the combined drugs for48hours, PPO andVEGF decreased obviously. The comparison of the combined group and the monotherapygroup has statistics significance. however, there is no obvious difference of the effectbetween As2O3and the combined group on PPO, P＞0.0083.【Conclusion】When treated by As2O3and VC for a certain time, the proliferation of human lungadenocarcinoma A549f would be inhibited by them at a certain concentration. Also theycan induce the apoptosis of the target cells and show dependence on time andconcentration. The inhibition ratio of the combined group is higher than that of As2O3and VC group. As2O3induces the apoptosis of the target cells by detained them at G2/Mphase. VC induces the apoptosis of the target cells by detained them at G0/G1phase.As2O3inhibit the growth of tumor by downturning VEGF and PPO genes. Themechanism of the antitumor of VC may be the downturn of VEGF, so as to treat cancer. |
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