Inhibitory Effect Of Chondroitin Sulfate On Colorecral Cancer And Its Mechanism

Colorectal cancer is one of the most common malignant tumors in digestive system,and its incidence rates continuously increased in China during the last decades.The early symptoms of colorectal cancer are not obvious leading to the high rates of middle and late stage tumors,seriously affecting the survival rate and living quality of patients.The feature of the long latency period provides the possibility of reducing the risk of its occurrence by dietary intervention.Therefore,the development of edible functional food has broad application prospects.Sturgeon has high nutritional value and contains a variety of bioactive components,especially chondroitin sulfate,which is highly rich in the bone and has a variety of physiological functions.In this study,in vivo and in vitro experiments were conducted to explore the growth inhibition of sturgeon chondroitin sulfate on colorectal cancer cells.Furthermore,we analyzed the possible signaling pathway of sturgeon chondroitin sulfate on cancer cell proliferation,in order to provide a new basis for the development of medicine feeding anticancer food.Specific research contents and results are as follows:1 The effects of chondroitin sulfate on the proliferation and apoptosis of three colorectal cancer cells(Caco-2,SW480 and HCT-116)were studied by cell model.The results showed that,compared to the positive control of 5-fluorine urea pyrimidine,the proliferation activity of sturgeon chondroitin sulfate on colorectal cancer cells of three strains had obvious inhibitory effects,and the maximum inhibition rate reached 70.94%,75%and 90%respectively.The effect of cell cycle arrest is G0/G1 phase in colorectal cancer cells,when the concentration was up to 400 g/mL,the proportion of Caco-2 in G1 phase increased from 41.72 to 61.39%,SW480 increased from 44.68%to 83.58%,HCT-116 increased from 36.31%to 88.56%.The microscope and confocal laser observation showed that the cancer cell chromatin pyknosis and cell rupture by chondroitin sulfate treating.The cell apoptosis was detected by flow cytometry,which showed that the total number of Caco-2,SW480 and apoptosis of HCT-116 cells increased 4 times,4.2 times and 7 times respectively by 400?g/mL of sturgeon chondroitin sulfate.The apoptosis activity of three kinds of colorectal cancer cells was enhanced after treatment with chondroitin sulfate by detecting enzyme activity of Caspase 3.The results showed that chondroitin sulfate could inhibit the proliferation and promote the apoptosis of colorectal cancer cells in vitro.2 The model of colorectal cancer mice induced by subcutaneous injection of tumor cell HCT-116 was used to evaluate the effect of sturgeon chondroitin sulfate on colorectal cancer in mice..It could slow down the growth rate of colon cancer tissue,reduce the expression of proliferating cell nuclear antigen(PCNA)in colon cancer tissue,and increase the activity of apoptosis.The results showed that the chondroitin sulfate of sturgeon had the function of inhibiting colorectal cancer cells in vivo.3 We explore the effect of sturgeon chondroitin sulfate on colorectal cancer cells through the detection of colorectal cancer cells and apoptosis of mouse tumor tissue in the key genes of transcription by q-PCR technology.In vitro experiments showed that sturgeon chondroitin sulfate could damage the intracellular DNA and the variation of the structure,result the up-regulation of p53 gene expression.After treatment by chondroitin sulfate 400?g/mL,the transcription level of P53 was increased 9.8 fold;the Bcl family of Pro apoptotic gene Bad and Bax were increased 8 times and 7.5 times;the expression of anti apoptosis gene Bcl-xl and Bcl-2 were decreased by 0.3 times and 0.2 times;the cytochrome C expression was increased 11 times,.At the same time,the Caspase family was activated.While the family of Caspase activity and gene expression were changed,which induced cell apoptosis.In vivo experiment results also showed that the sturgeon chondroitin sulfate could make the colon tumor related gene expression change,and modulate the activity of tumor cell proliferation and apoptosis by Bcl and Caspase family.Therefore,the sturgeon chondroitin sulfate could be used for treatment of colorectal cancer.