The Verification Of The Differentiated Gene Expression Of Multi-drug Resistance In Ovarian Cancer

Ovarian cancer is one of the most common malignant tumor in women.The majority of ovarian cancers are diagnosed in their advanced stage and the relative 5-year survival rate is low.To explore the mechanism of multiple drug resistance in ovarian cancer,The differentiated gene expression have further determined by FDD-PCR(fluro differentiated display PCR)method by the project team in prior period.The results showed①S4:Homo sapiens mitochondrion②a17:5-methyltetrahydrofolate-homocysteine methyltransferase reductase③actin-related protein 3 homolog mRNA④s16:ribosomal protein L35a mRNA⑤s20:replication protein A2 mRNA⑥s23:basic transcription factor 3(BTF3)mRNA⑦a5:thymosin,heta10(TMSB10)mRNA⑧a13:esterase D/formylglutathione hydrolase(ESD)⑨a26:mitochondrion differentiat expressed in resistant and sensitive ovarian cancer cells,we further studied these differentiated gene and P73,WWOX expression in resistant and sensitive ovarian cancer cells,and investigated the relationship between these genes and the multi-drug resistance and clinical pathology in ovarian cancer.At last,we researched the WWOX gene expression in the cisplatin resistant cells.1,The different genes expressed in the cisplatin resistant and sensitive ovarian cancer cells:RT-PCR and Northern blot methods were applied to determine the different genes expressed in the cisplatin resistant and sensitive ovarian cancer cells.The result showed only four genes(a17,a32,s23,s16)were investigated by Northern blot.the a17 and a32 only expressed in the drug-resistant ovarian cancer cell,but s16 and s23 gene expressed in some drug-resistant and sensitive ovarian cancer cells,the result implied these genes has the connection with the drug resistance,we presumed the a17 induce the drug resistance by increasing the drug metabolization,the s16 lead to the drug resistance by increasing the cell toxicity.Because we didn't have the biological message of the a32 and s23 gene,so we can't speculate the function.2,The expression and clinical value of these different genes in the ovarian cancer organization:RT-PCR method was applied to verify the gene expression in the tumor organization and the nomal organization,in order to probe which the expression of these different genes have the relationship in the clinical drug-resistance or not,and to analyze the clinical significance.The resulti showed that the high expression of S4,S16,S20,S23,a5,a26,a13,a32 genes hayed the connection with the cisplatin reststance in the ovarian cancer.We presumed that a13\a17 induce the drug resistance by increasing the drug metabolization,a26 lead to the drug resistance by inhibiting cancer cell atopotisize and change the penetrability of mitochondrial membrane,s16 conduce the resistance by increasing the cell toxicity,s20 cause the resistance by restorating the DNA damage.But we can't speculate the function of a5,a17,s4,a32,s23.Besides,the high expression of S4,S23,a5,a13,a32 haved the connection with the metastasis and progress in the ovarian cancer,a17,a26,s16,s20 haven't the association with clinical pathology.3,P73 gene express in the ovarian cancer organization and drug-resistance cell:RT-PCR and Northern blot methods were applied to determine the different genes expressed in the cisplatin resistant and sensitive ovarian cancer cells and organization,in order to investigate the relationship between P73 and the multidurg resistance and the clinical value.The result showed that there is a distant connection between the gene and clinical pathology.P73 expressed highly in the drug-resistance ovarian cancer,we considered that whether had the p53 mutation or not,the mutation induced the drug-resistance to occur.4,wwox gene express in the ovarian cancer organization and drug-resistance cell:RT-PCR and Northern blot methods were applied to determine the different genes expressed in the cisplatin resistant and sensitive ovarian cancer cells and organization,in order to investigate the relationship between wwox and the multidurg resistance and the clinical value.The RT-PCR result showed that WWOX expressed highly in the ovarian cancer drug-sensitive cell A2780 than the drug-resistanceA2780/SB/KB/TS,the result hints that wwox cann' t induce the multi-drug resistance,hut wwox expressed highly in the drug-resistance cell SKOV3/SB/KB/TS than drug-sensitive,the result was opposite to the prior conclusion,we considered that the phenomenon be related to the two cells' respective resistance indexes.Norther blot showed wwox expressed in the drug-sensitive cell highly than the durg-resistance cell,the conclusion implied that wwox hadn't have the relation to the chemotherapy resistance in ovarian cancer.Besides,wwox expressed highly in the cisplatin ovarian cancer organization,but it haven' t the statistics value.The research result haven' t consider wwox is a tumor suppressor,but suggest wwox has the relation with the occur and progress in the ovarian cancer.5,wwox gene's research in vitro by RNAi:RNA interference(RNAi)was used to explore the ways to reverse the multidurg-resistance in ovarian cancer,in order to restore the chemotherapy sensation.And further stugy whether wwox is a tumor suppressor or not,the research will provide the new train of thought for the gene diagnose and treatment.The result showed that wwox siRNA reduced the resistance indexes of SKOV3 SB,supposed that wwox had induced the drug-resistance by restorating the DNA damage,resisted chemotherapy drug' s damage and played a important role in drug pumb.But the result will be further vertificate by expression vector.From our result,we have come to the conclusion that some gene which are in relationship with multidrug resistance in ovarian cancer,and presumed the way these gene induced the drug-resistance,But it is only a hypothesis,we felt it reasonable to suggest that efforts should be made to construct an ideal computer model of drug resistance,with all possible concerned factors identified, verified,and included,which would be the essential preparation for future individualized management and satisfying reverse technique for those patients with resistant malignancy of ovary.