Effect of 5-Aminosalicylic Acid on Cell Proliferation,Apoptosis and Cell Cycle in Human Colon Cancer Cell Line HT-29 / 胃肠病学

Background:Ulcerative colitis-associated colorectal cancer(UcCRC)is the most serious complication of ulcerative colitis(UC). 5-Aminosalicylic acid(5-ASA)could reduce the risk of UC progressing to UcCRC. Aims:To investigate the effect of 5-ASA on cell proliferation,apoptosis and cell cycle in human colon cancer cell line HT-29 for verifying the inhibitory effect of 5-ASA on UcCRC. Methods:HT-29 cells were treated with different concentrations(0,10,20,30, 40 mmol/ L)of 5-ASA. Cell proliferation was measured by CCK-8 assay. Cell apoptosis was determined by TUNEL method. Cell cycle was analyzed by flow cytometry. Expressions of cell mitotic regulators AuroraB and BubR1 were determined by immunohistochemistry. Results:Proliferation inhibition rates and apoptosis rates of HT-29 cells in 5-ASA 10,20,30,40 mmol/ L groups were increased with increase in concentration of 5-ASA(P ﹤ 0. 05). Proportions of cells in phase G0 / G1 in 5-ASA 30,40 mmol/ L groups were significantly lower than those in 5-ASA 0,10,20 mmol/ L groups (P ﹤ 0. 05);proportions of cells in phase S in 5-ASA 0,10,20,30 mmol/ L groups were significantly lower than that in 5-ASA 40 mmol/ L group(P ﹤ 0. 05);while proportions of cells in phase G2 / M in 5-ASA 30,40 mmol/ L groups were significantly higher than those in 5-ASA 0,10,20 mmol/ L groups(P ﹤ 0. 05). Mean optical density(MOD)values of AuroraB and BubR1 were decreased with increase in concentration of 5-ASA(P ﹤ 0. 05). Concentration of 5-ASA was positively correlated with proliferation inhibition rate and apoptosis rate of HT-29 cells(P ﹤ 0. 05),but was negatively correlated with MOD values of AuroraB and BubR1( P ﹤ 0. 05). MOD values of AuroraB and BubR1 were negatively correlated with proliferation inhibition rate and apoptosis rate of HT-29 cells as well as proportion of cells in phase G2/ M (P ﹤0. 05),but were positively correlated with proportion of cells in phase G0/ G1(P ﹤0. 05). MOD value of AuroraB was positively correlated with MOD value of BubR1(P ﹤ 0. 05). Conclusions:5-ASA can inhibit proliferation and induce apoptosis in HT-29 cells,the mechanism may be related to inhibiting expressions of AuroraB and BubR1 and the resulted effect on cell cycle.

Cross-talk between BubR1 expression and the commitment to differentiate in adipose-derived mesenchymal stem cells

BubR1 mitotic checkpoint kinase monitors attachment of microtubules to kinetochores and links regulation of the chromosome-spindle attachment to mitotic checkpoint signaling. Defects in BubR1-mediated signaling severely perturb checkpoint control and are linked to diseases such as cancer. Studies using BubR1 mouse models suggest that BubR1 activities prevent premature aging and infertility. In this study, we show that BubR1 depletion in human adipose-derived mesenchymal stem cells (ASCs) precedes loss of the differentiation potential and induction of replicative senescence. These effects occur independently of p16(INK4A) expression and may involve DNA methylation. Our results reveal a new and unsuspected feature of BubR1 expression in regulation of adult stem cell differentiation.

Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma / 现代生物医学进展

Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.

Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma / 现代生物医学进展

Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.

Correlation between over expression of BUBR1 and chromosomal instability in colorectal carcinoma / 现代生物医学进展

Objective:Over expression of BUBR1 protein was reported in several human malignancies,however whether BUBR1 plays a role in chromosomal instability phenotype remains in controversy.This study was to explore the roll of BUBR1 protein in CIN phenotype in CRC.Methods:BUBR1 expression was studied immunohistochemieally in a panel of 93 advanced sporadic eolorectal cancers.Microsatellite status was evaluated by high resolution microsatellite analysis assay,TP53 gene mutation by direct sequencing and DNA ploidy by laser scanning cytometery.The relationship between BUBR1 overexpression and TP53 gene mutation,mierosatellite status,and DNA ploidy were studied.Results:BUBR1 overexpression was confirmed in 69% of cases.The overexpression was more frequent in tumor without high frequency microsatellite instability (P＜0.01) and TP53 mutation (P＜0.05).There was no statistic correlation between DNA aneuploidy and BUBR1 overexpression; however,a tendency that aneuploidy tumors had higher percentage of BUBR1 overexpression was shown.BUBR1 overexpression was not statistically related with clinieopathological factors.Conclusion:The linkage between BUBR1 overexpression and molecular factors indicating a CIN background implied that BUBR1 overexpression was indeed related with chromosomal instability in colorectal cancer.