ABSTRACT
Objective To investigate the inducing effects and related pathways of selenium dioxide ( SeO2 ) on the apoptosis in 2 human cervical carcinoma cell lines of high risk HPV subtypes .Methods HeLa (HPV-18-positive) and Caski (HPV-16-positive) cells were incubated with different concentrations of SeO 2 for 24 h respectively.Mor-phological changes of HeLa and Caski cells were observed under inverted optical microscope ;cell proliferation and activity were examined by MTT assay;flow cytometry was employed to detect the cell apoptosis;the expressions of apoptosis-related proteins caspase-3 and p53 in cervical carcinoma cell lines were determined by Western blot analysis;the effects of SeO 2 on apoptosis-related miRNA LET-7a expression was detected by stem-loop reverse tran-scription-polymerase chain reaction (RT-PCR).Results Cell morphology was obviously changed in vitro.Cells be-came rounded and shrunken .SeO2 markedly inhibited cell proliferation and viability in a dose-dependent manner in both cell lines; In HeLa cells the inhibitory effects induced by 7.5-30 μmol/L of SeO 2 were significant ( P<0.05);The inhibitory effects on Caski were statistical significant (P<0.05) even with low concentrations of SeO 2. The apoptosis induced by SeO 2 increased dose-dependently in cervical carcinoma cell lines , which were higher in Caski.SeO2 up-regulated the apoptosis-related proteins in cervical carcinoma cell lines .The expressions of caspase-3 and p53 in HeLa cells both significantly increased as compared with control group (P<0.05), and peaked at the concentration of 7.5 μmol/L.Treated with higher concentrations ( 7.5-30 μmol/L ) of SeO 2 , the expression on Caski cells increased significantly ( P<0.05 ) .SeO 2 induced of expression of apoptosis-related miRNA LET-7a both in HeLa cells and Caski cells with statistical meanings ( P<0.05 );the effects reached its peak at the concentration of 7.5 μmol/L bothly.Conclusions SeO2 shows anti-tumor properties via apoptosis pathway by up-regulating the expressions of apoptosis-related proteins caspase-3, the mechanisms of can be potentially explained by p 53 and LET-7a in cervical cancer cell lines.The apoptosis-inducing effect of SeO2 is more sensitive in HPV16+cell line compared with HPV18+cell line.