Basic & Clinical Medicine ›› 2017, Vol. 37 ›› Issue (12): 1712-1719.

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Selenium compound induces apoptosis of cervical carcinoma cells of high risk HPV subtypes

  

  • Received:2016-12-13 Revised:2017-03-15 Online:2017-12-05 Published:2017-11-29

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

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