观察5氮2′脱氧胞苷（5aza2′deoxycytidine ，又称5azaCdR）对卵巢癌细胞SKOV3和3AO增殖凋亡及DNA错配基因hMLH1 和hMLH2 表达的影响。方法： 以特异性甲基转移酶抑制剂5azaCdR 0.5、5、50 μmol/L处理人卵巢癌细胞SKOV3和3AO 3 d，继续常规培养7 d后，采用MTT比色法观察细胞经药物处理前后的增殖活性，用流式细胞术分析5azaCdR对细胞凋亡影响，以半定量逆转录聚合酶链反应（RTPCR）检测细胞经5azaCdR处理前后DNA错配修复基因hMLH1和hMSH2 mRNA表达水平的改变。结果： 人卵巢癌细胞SKOV3和3AO经5azaCdR处理后，与对照组比较,0.5、5、50 μmol/L均能明显抑制肿瘤细胞生长，随着5azaCdR浓度增加，细胞增殖速度下降。SKOV3经5azaCdR 0.5、5、50 μmol/L处理后细胞的凋亡率分别为（10.59±1.57）%、（17.52±1.72）%、（34.10±1.45）%，3A0经0.5、5、50 μmol/L 5azaCdR处理后细胞的凋亡率分别为（11.11±2.21）%、（17.24±1.11）%、（26.53±2.00）%，与对照组相比均有统计学意义（P<001）；且凋亡率与剂量成正相关（FSKOV3=227.6，P SKOV3<0.01； F3AO=108.4，P 3AO<0.01）。经5azaCdR处理后的两株卵巢癌细胞中hMLH1 和hMLH2 的mRNA表达量有不同程度的增加（P<0.01），且与药物存在剂量依赖性。结论： 〖JP2〗在人卵巢癌细胞株SKOV3和3AO中，5azaCdR可部分逆转hMLH1 和hMLH2 的失活，恢复其生长调控功能，抑制肿瘤细胞生长，并诱导细胞凋亡。

To observe the effect of 5aza2′deoxycytidine on proliferation and apoptosis of ovarian cancer cell lines (SKOV3 and 3AO) and on expression of mismatch repair (MMR) genes (hMLH1 and hMSH2) in SKOV3 and 3AO cells. Methods:Human ovarian cancer cell lines SKOV3 and 3AO were treated for 3 d with 5azaCdR (0.5, 5, 50 μmol/L), a specific demethylation agent, and then cultured in RPMI 1640 medium for another 7 d. The cells growth was observed by MTT assay before and after 5azaCdR treatment and the cell apoptosis was analyzed by flow cytometry. The expression of hMLH1 and hMSH2 mRNA was examined by semiquantitative reverse transcription polymerase chain reaction (RTPCR). Results: 5azaCdR (0.5, 5, 50 μmol/L) obviously inhibited the growth of SKOV3 and 3AO cells compared in a concentration dependent manner. The apoptosis rates of SKOV3 cells were (10.59±1.57)%, (17.52±172)%, (34.10±1.45)% after treated with 0.5, 5, 50 μmol/L 5azaCdR, respectively; and the apoptosis rates of 3AO cells were (11.11±2.21)%, (17.24±1.11)%, and (26.53±2.00)%, respectively, which were all markedly higher than those of control group（P <0.01）. We also found that the apoptosis rate was positively correlated with 5azaCdR concentration（FSKOV3=227.6，PSKOV3<0.01； F3AO=108.4，P3AO<0.01）. 5azaCdR treatment also increased the expression levels of hMLH1 and hMSH2 mRNA in a concentrationdependent manner (P <0.01). Conclusion: In human ovarian cancer cell line SKOV3 and 3AO，5azaCdR can partially reverse the deactivation of hMLH1 and hMSH2 of MMR genes and help hMLH1 and hMSH2 regain their function of growth regulation, thus inhibit the proliferation of tumor cells and induce cell apoptosis.

R730

山东省优秀中青年科研基金（No.2005BS03013）