| OBJECTTo study the effect of DNA methyltransferase inhibitor,5-aza-2'-deoxycytidine (5-Aza-CdR) combines with Paclitaxel which is usually used in the gastric cancer on the moderately differentiated gastric cancer cell line SGC-7901 and poorly differentiated gastric cancer cell line BGC-823.The effects include cells proliferation inhibition,blockaged—cycle, apoptosis and the expression of the anti-oncogene PTEN mRNA and E-cadherin mRNA.In order to study the effect of the different cycle-active drugs combination to the gastric cancer cells.METHODSSingly or associated use two medicines to intervene in different groups.To compare the proliferation inhibition through methyl thiazolyl tetrazolium(MTT).To contrast the apoptosis and blockaged cell cycle by flow cytometer(FCM),use RT-PCR to analyze the influence on the expressions of anti-oncogene PTEN mRNA and E-cadherin mRNA.RESULTS1.After two medicines' associated using,the inhibition ratio of the BGC-823 is 75.36%,and the inhibition ratio of SGC-7901 is 82.18%.It is observed obviously that there is a conspicuous synergistec effect when combined two medicines.In the BGC-823 gastric cancer cell,the IC50 of the Paclitaxel is 4.67×10-8mol/L,well its IC50 on the the moderately differentiated gastric cancer cell line SGC-7901 gastric cancer cell is 1.68×10-9mol/L.And the IC50 of 5-Aza-CdR on the poorly differentiated gastric cancer cell line BGC-823 cells is 4.13×10-4mol/L,but on the the moderately differentiated gastric cancer cell line SGC-7901 cells is 8.96×10-6mol/L.2.In addition,according to FCM,the Paclitaxel can make the cell cycele stopped at G2/M stage,and 5-Aza-CdR can stop it at S stage.When we combine two medcine,the cell cycle can be stopped at each G2/M and S stage,and the cell apoptosis rate is also raised.3.In the process of detecting the expressions of the anti-oncogene PTEN mRNA and E-cadherin mRNA,we can observe that Paclitaxel has no effect,while 5-Aza-CdR can make the anti-oncogene expressed.After combined the Paclitaxel and 5-Aza-CdR,It obviously increases the amount of the expression of the PTEN mRNA and E-cadherin mRNA rather than the amount when used 5-Aza-CdR only.It explained that the Paclitaxel can promote the effect of the 5-Aza-CdR on the anti—oncogene.CONCLUSIONS(1) 5-Aza-CdR and Paclitaxel have effect on the moderately differentiated gastric cancer cell line and poorly differentiated gastric cancer cell line when singly used,and combination of them has synergistic effect.(2) 5-Aza-CdR can stop the cell cycle at S stage,and Paclitaxel can block the cell cycle at G2/M stage.When combined,the cell cycle is blocked at each S and G2/M stage,and the apoptosis rate is increased.(3) the Paclitaxel can promote the effect of the 5-Aza-CdR on the anti—oncogene PTEN mRNA and E—cadherin mRNA.
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