Expression Of Notch Receptor In Human Cervical Cancer And The Effects Of Curcumin

Objective:The Notch family of cell surface receptors plays a key role in cell-fate determination and differentiation,functioning in a cell- and context-specific manner. In many kinds of cells, Notch activation is generally thought to maintain stem cell potential and inhibit differentiation, thereby promoting carcinogenesis. Notch activation is oncogenic in many instances.It is confirmed that there is an activation of Notch signaling pathway in cervical cancer in contrast with normal cervical tissue,so some scientists persume its connection with the carcinogenesis and development of cervical cancer .Curcumin, a polyphenolic compound extracted from rhizomes of Curcuma species, has in fact been shown to possess potent antiinflammatory and antiproliferative and proapoptotic effects in many kinds of cells,which appear to be linked to its ability to suppress some signaling pathway .Here, we have examined the expression of Notch1 in both human cervical cancer tissue and normal cervical tissue.Further, we have investigated the potential antiproliferative effects of Curcumin in Hela cells to see its contri- bution to the expression of Notch signaling pathway and also the NF-kB in order to showe some cross-talk between NF-kB and Notch signaling pathway, which also means to find out the molecule mechanisms of the antiproliferative effects of Curcumin.Method:Cell culture ; The viability of cells was measured by MTT assay ; Observe cell morphology change in the administration process ; The expression of Notch1,Notch2,Bcl-2,Bax mRNA were evaluated by reverse transcriptase- polymerase chain reaction (RT-PCR)analysis. The expression of Notch1 in both cervical cancer tissue and normal cervical tissue were evaluated by reverse transcriptase-polymerase chain reaction (RT-PCR)analysis. Protein levels of P65 was detectted by Western Blotting.Result:1. MTT assay showed that Curcumin can decease the survival rate of Hela cells in a dosage-time dependent mode .2.RT-PCR results indicated , there is a activation of Notch1 in cervical cancer tissue. In Hela cells Curcumin downregulated the constitutive express- ion of Notch1,Notch2,Bcl-2 genes, but upregulated the expression of Bax and the ratio of Bcl-2/Bax decreased in Hela cells. There is no significance in the expression of IkB mRNA .3. Western Blotting results manifested that Curcumin downregulated the expression of P65.Discussion:Our data showed persistent deregulation of Notch1 during cervical cancer progression based on the RT-PCR analysis which is consistent with other researchers .We presume that Notch signaling pathway is connected with the carcinogenesis and development of cervical cancer .RT-PCR results indicated that in Hela cells Curcumin downregulated the constitutive expression of Notch1,Notch2. inhibite the expression of NF-kB and the apoptotic protein such as Bcl-2 which is one of the downstream target genes of NF-kB.It has determined that NF-kB is one of the downstream target genes of Notch signaling pathway,so we suppose that the antiproliferative of Curcumin is associated with its ability to downregulate the NF-kB and apoptotic proteins,which is resulting from its inhibition of Notch signaling pathway.Furthermore,we also observed that there is no significance in the expres- sion of IkB mRNA .We suppose that Curcumin can also downregulated IKK activities,avoiding the degradation of IkB.Conclusion:(1) Notch signaling pathway may be associated with the carcinogenesis and development of cervical cancer .(2) Curcumin suppress Hela cells through Notch signaling pathway .(3) The antiprolaferation and proptotic effects of Curcumin is associated with its ability to downregulate the expression of NF-kB by suppress Notch signaling pathway .(4) Curcumin can downregulate direct or indirect the expression of Bcl-2。(5) Curcumin can also downregulated IKK activities,avoiding the degradation of IkB.(6) Curcumin may be a potent and potential antitumor drug.