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Effects of 5aza2′deoxycytidine on apoptosis of ovarian cancer cells and on expression of mismatch repair genes
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Abstract:
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±172)%, (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.
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Clc Number:
R730
