Effect Of 6-shogaol On The Expression Of E6TP1,galanin And Galr 2 MRNA In Human Cervical Cancer Cells

Background and objectives:Cervical cancer is one of the most common malignancies in developing countries.perineural invasion(PNI)is one of the causes of poor prognosis and recurrence of this type of patient.As a tumor suppressor protein,E6 targeting protein 1(E6TP1)can be degraded by E6 protein through the ubiquitin proteasome pathway,activation of Rap1 Pathway leading to Proliferation and Metastasis of tumor cells,which induces the occurrence and development of cervical cancer.Galanin can stimulate the up-regulation of GalR2 in tumor cells and produce prostaglandin E2(PGE2),PGE2 as an effective motor factor to stimulate the invasion and metastasis of tumor cells.In the feedback mechanism,Galanin released by tumor cells can induce the formation of neuronal processes and the interaction between nerve and tumor cells,thus promoting the occurrence of PNI.Some scholars have found that E6TP1 can be degraded by E6 protein via the ubiquitin proteasome pathway,which can up-regulate the expression of Galanin and GalR2 in HPV positive human cervical cancer cell lines.Studies have shown: 6-shogaol(6S)could block the cells at G2/M phase,and inhibit the growth of cervical cancer cells.In this study,the expression of E6TP1,Galanin and GalR2 in cervical cancer cell Caski cells and C33 A cells after 6S treatment was detected and preliminarily investigated the effect of 6S on PNI of cervical cancer cell line.Methods:The expression of E6TP1,Galanin and GalR2 mRNA were detected by RT-PCR after the treatment of 6-shogaol on human cervical cancer(Caski cells and C33 A cells)lines in vitro for 2h or 6h.Results:E6TP1 Galanin and GalR 2 were all expressed in human cervical cancer cell(Caski cells and C33 A cells);In human cervical cancer cells(Caski cells and C33 A cells),the expression of E6TP1 protein was up-regulated in the same concentration of 6-shogaol for 2 h or 6 h,compared with the corresponding control group,and increased gradually with the increase of the time of drug action and HPV positive Caski cells were significantly up-regulated than HPV negative C33 A cells.The difference was statistically significant(P<0.05);In human cervical cancer cells(Caski cells and C33 A cells),the expression of Galain was down-regulated in the same concentration of 6-gingingenol for 2 h or 6 h,compared with the corresponding control group,and decreases gradually with the increase of the time of drug action and HPV positive Caski cells were significantly down-regulated than HPV negative C33 A cells.The difference was statistically significant(P<0.05);In human cervical cancer cells(Caski cells and C33 A cells),the expression of GalR2 was down-regulated in the same concentration of 6-gingingenol for 2 h or 6 h,compared with the corresponding control group,and decreases gradually with the increase of the time of drug action and HPV positive Caski cells were significantly down-regulated than HPV negative C33 A cells.The difference was statistically significant(P<0.05).Conclusions:The expression of E6TP1 was upregulated by 6-shogaol on human cervical cancer cells,which had a certain anti-virus effect on HPV;6-shogaol act on Caski cells which are HPV positive cells of cervical cancer can significantly up regulate E6TP1 expression and down regulate galanin and GalR2 expression,suggesting that 6-shogaol can regulate the expression of E6TP1?galanin and GalR2 in cervical cancer PNI,effects of galanin and GalR2,thereby inhibiting cervical cancer PNI development.