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The Effect Of IP6+ Inositol On Epithelial Ovarian Cancer SKOV3cells Migration?Invasion And Wnt/?-catenin Signaling Pathway

Posted on:2018-10-02Degree:MasterType:Thesis
Country:ChinaCandidate:X ZhouFull Text:PDF
GTID:2334330536963593Subject:Obstetrics and gynecology
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Objective:Ovarian cancer mortality rate is in the first place of gynecological malignancy.And 85%-90% of them are epithelial ovarian cancers.Because ovarian cancer has no specific symptoms,and the lack of high sensitivity and high specificity screening methods and targeted treatment of malignant tumors,and the traditional chemotherapy there are a lot of side effects and chemotherapy drug resistance,so that the survival rate of ovarian cancer is still Very low.Natural medicines have the advantages of economic,efficient,low toxicity,wide source and so on.In recent years,phytophosphate(IP6),with it's anti-cancer effect,become a recent hot spot.Wnt pathway has recently been widely concerned,it can regulate animal tissue differentiation,organ formation and other physiological processes,access to key protein expression abnormalities,can lead to cancer.Among them,?-catenin and T-cell factor 4(TCF4)are the main members of Wnt pathway.It has also been shown that the expression of ?-catenin in ovarian cancer is generally higher than that in ovarian benign tumor and normal ovary,and the histological type,tumor stage,tumor cell infiltration and metastasis of ovarian cancer are closely related to the abnormal expression of ?-catenin.TCF4 and ?-catenin can promote gene transcription,and the development of many tumors are related to TCF4.Epithelial mesenchymal transition(EMT)is a process of cell transformation-from epithelial to interstitial.Wnt classical pathway is closely related to EMT,and ?-catenin,TCF4 is closely related to the occurrence of EMT and tumor invasion and metastasis.And the relationship between IP6 +inositol and Wnt/?-catenin signaling pathway is not clear in ovarian cancer.This study aims to explore the IP6 + inositol on ovarian cancer invasion andmetastasis ability and Its mechanism of action.And if the combined use of cisplatin and IP6 + inositol on ovarian cancer have a synergistic effect or not?Methods:1 Transwell tumor cell invasion experiments to observe the effect of IP6+ inositol in vitro on the invasion and metastasis of ovarian cancer cells.2 Western blot detect the effect of IP6 + inositol on Wnt / ?-catenin signaling pathway.3 RT-PCR was used to detect the expression of ?-catenin and TCF in the Wnt pathway4 Statistical methods: SPSS21.0statistical software to deal with experimental data.Results:1 Transwell invasion experiment showed that the number of cells in the combined group was 26.2 ± 2.6,the number of cells in the cisplatin group was32.0 ± 3.4,the number of cells was significantly lower than that of the control group 82.8 ± 5.7,the difference was significant(P<0.05),The number of cells in the IP6 + inositol high and medium dose group was 62.6 ± 2.3 and 73.2 ±3.0,respectively,compared with the control group,the difference was statistically significant(P<0.05).IP6 + inositol low dose group was 80.2 ± 3.3,compared with the control group,the difference was not statistically significant(P>0.05),IP6+inositol concentration group,with the IP6 concentration increased the number of cells decreased,the difference was statistically(P <0.05).2 Western blot was used to detect the expression of ?-catenin protein:0.886±0.262 and 0.987 ± 0.707 in the high and middle dose groups of IP6 +inositol,which was significantly higher than that in the control group 1.291 ±0.431(P <0.05).IP6 + inositol low dose group was 1.245 ± 0.580,compared with the control group no significant difference(P>0.05).With the increase of IP6+inositol dose,the protein expression of each group was decreased gradually,the expression of combination group was 0.601±0.019 and in cisplatin group was 0.694 ± 0.039,the difference was statistically significant(P <0.05).And the expression of combination group was lower than that of cisplatin,the difference was statistically significant(P <0.05).3 The expression of ?-catenin mRNA was detected by RT-PCR: 1.000 ±0.000 in the control group and 0.984 ± 0.103 in the low dose of IP6 +inositol,there was no statistically significant(P> 0.05),IP6 middle dose group and high dose group,DDP group,combination group,the expression was0.906 ± 0.010,0.786 ± 0.104,0.570 ± 0.123,0.488 ± 0.126,Compared with the control group,the difference was statistically significant(P<0.05).The combination group is lower than DDP group,the difference was statistically significant(P <0.05).IP6 dose group,with the dose increased,the expression gradually decreased,the difference was statistically significant(P <0.05).4 The expression of TCF4 mRNA was detected by RT-PCR: 0.793 ±0.341 in the high dose of IP6 +inositol,0.853 ± 0.148 in the middle dose group and 0.985 ± 0.133 in the low dose group,compared with 1.000 ± 0.000 in the control group,the low dose group was no statistically significant(P>0.05).Compared with the high and middle dose groups,the difference was statistically significant(P<0.05).With the increase of IP6 dose,mRNA expression gradually weakened.Conclusions:1 IP6 + inositol can inhibit the invasion and metastasis of ovarian cancer SKOV3 cells.2 IP6 + inositol and cisplatin have synergistic anti-cancer effect.3 Mechanism of IP6 + Inositol on Invasion and Metastasis ability of Ovarian Cancer may inhibit the EMT of tumor cells and affect the Wnt / ?-catenin signaling pathway,and ultimately inhibit the invasion and metastasis.
Keywords/Search Tags:Ovarian Cancer, SKOV3, IP6+Inositol, Wnt Pathway, ?-catenin
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