关键词: 二氧化硒（SeO2）, 高危HPV亚型, 凋亡, miRNA, LET-7a

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 of HPV subtypes. Methods HeLa (HPV-18-positive) and Caski (HPV-16-positive) cells were treated with different concentrations of SeO2 for 24 h respectively. Morphological 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 SeO2 on apoptosis-related miRNA LET-7a expression was detected by Stem-loop reverse transcription-polymerase chain reaction (RT-PCR). Results Cell morphology was changed obviously in vitro. Cells became 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 SeO2 were significant（P＜0.05）; The inhibitory effects on Caski were statistical significant（P＜0.05） even in low concentrations of SeO2. The apoptosis rates induced by SeO2 increased dose-dependently in cervical carcinoma cell lines, which were higher in Caski. SeO2 could up-regulate the apoptosis-related proteins levels in cervical carcinoma cell lines. The expressions of caspase-3 and p53 in HeLa cells both significantly increased 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 SeO2, the expression on Caski cells increased significantly (P＜0.05). SeO2 could induce the expression of apoptosis-related miRNA LET-7a both in HeLa cells and Caski cells with statistical meanings (P＜0.05); the induction effects reached its climax 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 involve inducing effects of p53 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.

Key words: Selenium Dioxide (SeO2), High Risk of HPV Subtypes, Apoptosis, miRNA, LET-7a