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Parthenolide Inhibits Angiogenesis in Esophageal Squamous Cell Carcinoma Through Suppression of VEGF
Balsalazide is an anti-inflammatory drug used in the treatment of inflammatory bowel disease. Balsalazide can reduce inflammatory responses via several mechanisms, including inhibition of nuclear factor-κB (NF-κB) activity. Parthenolide (PT) inhibits NF-κB and exerts promising anticancer effects by promoting apoptosis. The present investigated the antitumor effects of balsalazide, combined with PT, on NF-κB in a representative human colorectal carcinoma cell line, HCT116.
We counted cells and conducted annexin-V assays and cell cycle analysis to measure apoptotic cell death. Western blotting was used investigate the levels of proteins involved in apoptosis.
PT and balsalazide produced synergistic anti-proliferative effects and induced apoptotic cell death. The combination of balsalazide and PT markedly suppressed nuclear translocation of the NF-κB p65 subunit and the phosphorylation of inhibitor of NF-κB. Moreover, PT and balsalazide dramatically enhanced NF-κB p65 phosphorylation. Apoptosis, through the mitochondrial pathway, was confirmed by detecting effects on Bcl-2 family members, cytochrome c release, and activation of caspase-3 and -8.
Combination treatment with PT and balsalazide may offer an effective strategy for the induction of apoptosis in HCT116 cells.
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Colorectal cancer (CRC) develops from colonic adenomas. Type 2 diabetes mellitus (DM) is associated with a higher risk of CRC and metformin decreases CRC risk. However, it is not certain if metformin affects the development of colorectal polyps and adenomas. This study aimed to elucidate if metforminaffects the incidence of colonic polyps and adenomas in patients with type 2 DM.
Of 12,186 patients with type 2 DM, 3,775 underwent colonoscopy between May 2001 and March 2013. This study enrolled 3,105 of these patients, and divided them in two groups: 912 patients with metformin use and 2,193 patients without metformin use. Patient clinical characteristics, polyp and adenoma detection rate in the two groups were analyzed retrospectively.
The Colorectal polyp detection rate was lower in the metformin group than in the non-meformin group (39.4% vs. 62.4%,
In patients with type 2 DM, metformin reduced the incidence of adenomas that may transform into CRC. Therefore, metformin may be useful for the prevention of CRC in patients with type 2 DM.
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