Growth Inhibitory And Induction Of Apoptosis Of Caski,Hela And C33A Cells By Nano-Realgar And Its Mechanism

Purposes:To investigate the proliferation inhibitory and apoptosis induction effects of nano-realgar on cervical cancer cell Caski (HPV16+, adeno carcinoma),Hela (HPV18+, squmous carcinoma) and C33A (HPV-, adeno carcinoma).Methods:Treat the cells with different concentration (5,10,20,40ug/ml) and time (24,48,72,96h)/(48h), observe the morphology under phase contrast microscope; MTT to test the growth inhibitory; flow cytometry to measure the percentage of apoptosis and different stages of cell cycles; real-time PCR for the measurement of the level of E6E7mRNA; immunohistochmistry for the detection of the level of E6and E7oncoprotein.Results:The cells' growth rates was decreased and they got more apoptosis on an concentration-time dependened behavior, what is more, Caski cells seems more sensitive to the drug where as the C33A cells were the last sensitive one; The flow cytometry test shows that the nano-realgar could induce more apoptosis as the concentration increased (P<0.05); high concerntration (20,40ug/ml) of nano-realgar can induce G2/M stage block; Real time PCR shows the level of E6and E7mRNA was decreased in an concentration depended behavior and the E6gene was inhibited more that E7gene and so as both the E6and E7gene of HPV16to HPV18; IHC shows the E6and E7oncoprotein was decreased as the concentration of nano-realgar increased.Conclusion:Nano-realgar can inhibit the growth and induce apoptosis on different kinds of cervical carcinoma cell line, the effects goes as follows Caski> Hela>C33A, it can also induce G2/M stage block on HPV positive cervical cancer cells when the concentration of drug is high enough (20,40ug/ml). The E6E7mRNA and oncoprotein may contribute to these effects, and E6may take the leading role.