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Ding's herbal enema (DHEP) is a traditional Chinese medicinal therapy that has been used to treat ulcerative colitis (UC) in China. The present study determined the molecular mechanism of the effect of DHEP in UC treatment. C57BL/6J mice were treated with 3.5% (w/v) dextran sulfate sodium (DSS) for 7 days to establish an animal model of colitis. The mice were divided into five groups (n=5): Control, vehicle, DHEP, mesalazine and ß-sitosterol. After oral administration for 7 days, the body weight, disease activity index, histopathology and inflammatory factors were analyzed. The fractions of CD4+Foxp3+ regulatory T (Treg) cells and CD4+IL-17A+ T helper (Th) cells were determined by flow cytometry. Gut microbiota composition was analyzed by next-generation sequencing. The results revealed that DHEP and ß-sitosterol could significantly alleviate the symptoms of DSS-induced UC. Furthermore, the levels of IL-6, cyclooxygenase-2, TNF-α and p65 were reduced after administration of DHEP. Additionally, the data indicated that DHEP could increase the abundance of seven operational taxonomic units (OTUs) and decrease the abundance of 12 OTUs in the gut microbiota. The content of short-chain fatty acids in the colon remodeled the balance of Treg/Th17 cells in DSS-induced UC in mice. The present study preliminarily defined the mechanism of action of DHEP in UC that may be associated with the regulation of the gut microbiota composition, and maintenance of the balance between Treg and Th17 cells. Furthermore, ß-sitosterol exhibited the same effects with DHEP and it could be a possible substitute for DHEP in UC treatment.
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INTRODUCTION: Circular RNAs (circRNAs), a novel class of non-coding RNAs, which are widely expressed in human cells, have essential roles in the development and progression of cancers. The aim of this study is to figure out the role of circ_000166 in colon cancer (CC) development and the signaling pathway involved. MATERIALS AND METHODS: HT29 and HCT116 cells were transfected with siRNA of circRNA, miRNA mimics and inhibitors. Cell proliferation, migration and invasion were examined using CCK-8 assay and transwell assay, respectively. Luciferase reporter assay was used to validate the targets of circRNA and miRNA. CC cells were implanted into nude mice subcutaneously to detect tumor growth. RESULTS: hsa_circRNA_000166 was significantly upregulated in the human CC tissue and in the CC cell lines. Knockdown of hsa_circRNA_000166 reduced cell viability, colony formation, migration and invasion in vitro and decreased tumor size and weight in vivo. Luciferase reporter assay revealed that miR-330-5p was the target of circRNA_000166. miR-330-5p could bind to 3' untranslated region (3'UTR) of ELK1 to downregulate both mRNA and protein expression of ELK1. Dual inhibition of circRNA_000166 and miR-330-5p inhibited the suppression of cell proliferation, migration and invasion induced by si-circRNA_000166. CONCLUSION: The data of this study demonstrated that the hsa_circRNA_000166 could upregulated the expression of gene ELK1 by sponging miR-330-5p, which may contribute to a better understanding of the regulatory circRNA/miRNA/mRNA network and CC pathogenesis.
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OBJECTIVE: To study the anticancer effects of tea polyphenols on colorectal cancer with microsatellite instability (MSI) in nude mice and to explore its mechanism. METHODS: A colostomy was performed on the caecum of nude mice. Tumor fragments collected from the subcutaneous tumor of hMSH2-absence colon carcinoma Lovo cell line were surgically implanted onto the submucosa of the caecum during colostomy to establish the model. Then, the nude mice were divided into untreated group and 50, 75 and 100 mg/kg tea polyphenols groups. The mice in tea polyphenols-treated groups were given intra-abdominal injection of 50, 75 and 100 mg/kg tea polyphenols respectively. The inhibition rates of tumors were calculated, and microsatellite instability (MSI) and the alteration of transforming growth factor-beta1 (TGF-beta1), TGF-beta2 and insulin-like growth factor (IGF) were detected by Genescan method at different times after the injection. RESULTS: The tumor volumes of the three groups began to decrease at the 1st week and decreased most greatly from 2 to 3 weeks after treatment, and then the tumors tended to increase. The study found that tea polyphenols could inhibit the tumor growth. The tumor inhibition rates in the three treated groups were significantly higher than those in untreated group 1, 2, 3 and 4 weeks after treatment (P<0.01). Detection of MSI showed that the colorectal tumor in the untreated group presented with four MSI signs, including BAT-25, D2S123, D5S346 and D17S250, and TGF-beta1, TGF-beta2, IGF expressions. After using the tea polyphenols, the microsatellite tended to become stable. CONCLUSION: Tea polyphenols can inhibit the mismatch-repair-gene deficient colorectal cancer in nude mice by down-regulating the microsatellite instability.