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Study On The Mechanism Of Low Dose Desitabine Inhibite The Proliferation Of High Microsatellite Instability Colorectal Cancer

Posted on:2019-10-28Degree:MasterType:Thesis
Country:ChinaCandidate:X Y JiangFull Text:PDF
GTID:2404330623455141Subject:Surgical Oncology
Abstract/Summary:PDF Full Text Request
Objective :(1)We want to know the difference of protein expression in colorectal cancer under different microsatellite conditions and the related genes.And we used Western Blot methodto detect the expression of SLC26A3,MYH11,ZG16,AQP8,CLCA4 and other proteins in colon cancer tissues of MSS and MSI-H groups.(2)Study on the mechanism of inhibition of proliferation of SW48 cells in colon cancer by low dose decitabine.Methods :(1)colon cancer tissues with different microsatellite states were identified by immunohistochemistry.(2)Western Blot was used to detect the expression of SLC26A3,MYH11,AQP8 and other proteins in colon cancer tissues of MSS and MSI-H groups,and to determine whether there were protein expression differences in the potentially significant target genes.(3)SW48 cells were divided into three groups,namely WT,5-FU and 5-FU+DAC groups.PBS,5-FU and 5-FU+DAC of different concentrations were respectively given.Cell proliferation activity was detected by CCK8 method to analyze whether these drugs could inhibit tumor cell proliferation and the lowest effective concentration could inhibit cell proliferation.Results : 1)The results of tissue microarray showed that the MSI-H/dMM tumors were mostly located in the rectum,and the histological types were mostly adenocarcinomas,and predominantly moderately differentiated,but the difference between the gender and age was not statistically significant.(2)Compared with normal tissues,MSI-H colon cancer tissues showed decreased expression of SLC26A3,MYH11,and AQP8 proteins.(3)The cell proliferation of 5-FU+DAC combination group was significantly inhibited,compared with the control group and 5-FU group.(4)We found that SLC26A3 expression was up-regulated after 5-FU and DAC treatment.Conclusion :(1)Changes in protein expression of SLC26A3,MYH11,and AQP8 may be related to MSI-H.(2)Low dose DAC+5-FU can inhibit the proliferation of SW48 cells,which may be one of the new therapeutic options for MSI-H colorectal cancer.
Keywords/Search Tags:colorectal cancer, DAC, MSI-H, chemosensitivity
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