| Colon cancer is a malignant tumor of the digestive tract that occurs well at the junction of the rectum and sigmoid colon.It is the age segment of 40~50 years old with high incidence of colon cancer.The incidence of the cancer is 1:2 to 3 in the incidence of women and men,and the third largest in the incidence of gastrointestinal cancer.At present,surgery combined with chemotherapy is the main treatment of colon cancer.Chemotherapy can improve the success rate of surgery,reduce the recurrence rate of the disease,and improve the survival rate of the patients.However,the effects of chemotherapeutic drugs on tumor cells can also cause different degrees of injury to normal tissue cells,which causes most colon cancer patients to give up or even die in the course of treatment.Therefore,searching for high efficacy and low toxicity anticancer drugs has become a hot topic of current research.Garlic is a common ingredient,but as early as the last year of the Eastern Han Dynasty medical records of garlic have been recorded.The "Compendium of Materia Medica" written by the Tang Dynasty physician Li Shizhen recorded that: garlic is warm and spicy;the spleen,stomach,and lungs are used.It has the functions of eliminating food in the temperature,stagnating air,warming the spleen and stomach,eliminating product,detoxifying and killing insects.Garlic is hailed as "penicillin grown in the ground" and "natural antibiotics" because garlic contains allicin.Diallyl disulfide(DADS)is an organic sulfur compound obtained after the decomposition of allicin.It has a strong garlic odor and presents a pale yellow liquid.It is insoluble in water and is a fat-soluble monomer compound.The current study found that the main effects of DADS include: detoxification,antibacterial,prevention of cardiovascular disease and protection against colon cancer.The first three kinds of effects have been widely known,but DADS is rarely mentioned in the research report of colon cancer.Histone deacetylase-1(SIRT1)is a member of the sirtuins family and is dependent on nicotinamide adenine dinucleotide(NAD+)in vivo and in various groups.Protein,non-histone,a histone deacetylase that regulates activity by deacetylation.SIRT1 is widely involved in the regulation of mammalian cell life signaling and metabolic pathways such as glucose metabolism and insulin secretion,and plays an important role in metabolic syndrome,apoptosis,cardiovascular disease,and neurodegenerative diseases.At the same time,SIRT1 has been mentioned in most of the literature related to tumors,such as leukemia,glioblastoma,prostate cancer,primary colorectal cancer,and skin cancer.SIRT1 is also significantly higher than normal skin tissue in squamous cell carcinoma and basal cell carcinoma.A large number of scientific researches have confirmed that in recent years,nuclear factor-kappaB(NF-?B),one of the nuclear transcription factors favored by the academic community,has been involved in the entire process of tumor cell disease,reproduction,division,death,and transmigration.Deacetylation of NF-?B can be achieved by NAD+-assisted SIRT1.I?B? can no longer react with NF-?B at this time,thereby blocking the nuclear localization signal and impeding the formation of specific genes such as tumor cell lesions and transmigration.In addition,MMPs are closely related to tumor invasion.The research report pointed out that SIRT1 is an inducing factor for the transcription and translation of MMP-9 gene in the MMPs family.It has also been reported that the synthesis of the MMP-9 gene in the nucleus can be regulated by direct binding of phosphorylated NF-?B to the MMP-9 promoter.The study steps are as follows: Colon cancer cell line HT-29 was first cultured in vitro,DADS was added at different doses of 0,30,60,and 120 ?mol·L-1,and culture was continued for 48 h.Different methods were used to detect the different responses of cells to HT-29 under DADS.Including CCK-8 method for detecting viability,Transwell method and Scratch method for detection of cell transfection in vitro,RT-PCR and Western Blot were detected in Nampt(10 ?g·L-1)and DADS(0,30,60,120 ?mol· Changes in SIRT1,NF-?B,and MMP-9 produced by L-1)doses.In the second step,cells HT-29 were injected into the abdomen of Balb/c mice raised in a 30-day-old test.After the tumors grown in the implanted cells grew to 5 mm in length,they were administered daily with a dose of(1 mg/Kg)DADS.One trial drug test was performed and a record of changes in body weight and tumor size of the test rats under the effect of daily drug was prepared.Samples were collected 28 days later.The number of colon cancer metastasis was counted.HE staining was used to record the shape of tumor cells.SIRT1,NF-?B/P65 and MMP-9 proteins were detected by immunohistochemistry and Western Blot.And make a record.The results show: 1.Ht-29 was effective in controlling the proliferation of cells(P < 0.05)after 48 h in DADS,respectively(30,60,90,120,150,mol· l-1),and there was a certain degree of dependence on drugs.2.DADS was able to inhibit the expression of SIRT1,mmp-9 mRNA and protein in ht-29 cells,and promote the expression of NF-in vitro B mRNA and protein.3.The results of internal statistical data and the use of HE staining tumor cells showed that DADS was able to effectively control the proliferation of tumor cells in mice and promote nuclear reduction in the cell.The data were as follows: the weight of the rats in the DADS group was(26.71 + 1.54)g,the tumor volume(841.98 + 112.51)mm3,the mass of the tumor(0.83 + 0.33)g;The corresponding data of the model group were(16.78 + 0.97)g,(1493.48 + 210.90)mm3,(2.85 + 0.97)g,and the statistical difference of the three sets of data(P < 0.01)was statistically significant.4.The experimental data showed that the NF-in the tumor cells of DADS was significantly improved under the influence of DADS,while SIRT1 and MMP9 were significantly reduced.The results of two different experiments in vitro and in vivo indicate that DADS can inhibit SIRT1 through the effect of SIRT1,stimulate the expression of NF-?B protein,and down-regulate the expression of MMP-9 to regulate the metastasis and apoptosis of colon cancer cells. |
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