Targeting of Notch, IL-1, and leptin has therapeutic potential in xenograft colorectal cancer

IF 1.1 4区 生物学 Q3 BIOLOGY
RUMEYSA ÖZYURT, NİLÜFER ERKASAP, METE ÖZKURT, SERDAR MUSTAFA ERKASAP, KONSTANTİNOS DİMAS, AYŞE ÇAKIR GÜNDOĞDU, ENGİN ULUKAYA
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引用次数: 0

Abstract

Background/aim: Colorectal cancer (CRC) is a fatal malignancy type and its occurence still needs to be explored mechanistically. Notch, IL-1, and leptin crosstalk is reported to play a role in the proliferation, migration, and expression of proangiogenic molecules. In this study, we aimed to investigate the effect of inhibition of Notch, IL-1, and leptin on CRC. Materials and methods: To generate colorectal cancer tumor xenografts, 1 × 107 cells from exponentially growing cultures of HCT15 cells were injected subcutaneously, at the axillary region of the left and right rear flanks of forty NOD.CB17-Prkdcscid/J (NOD/SCID) female mice. The mice were then monitored for the development of tumors and were randomly divided into five groups when tumor sizes reached a volume of approximately 150 mm3 . Mice were used to determine the effectiveness of the gamma-secretase inhibitor (DAPT, Notch inhibitor), the interleukin-1 receptor antagonist (Anakinra) and the leptin receptor antagonist (Allo aca) against tumor growth. The mice were euthanized by CO2 inhalation immediately after the treatments finished, and all efforts were made to minimize suffering. Tumors were excissed for RT-PCR and histological analysis. Results: There is an intact Notch, IL-1, and leptin signaling axis, and in vivo antagonism of Notch, IL-1, and leptin affects mRNA and protein expression of inflammatory and angiogenic molecules. Conclusion: Present data suggest that targeting Notch, IL-1, and leptin may be possesses therapeutic potential in CRC.
靶向Notch, IL-1和瘦素在异种移植结直肠癌中具有治疗潜力
背景/目的:结直肠癌(Colorectal cancer, CRC)是一种致死性恶性肿瘤,其发生机制仍需进一步探讨。据报道,Notch、IL-1和瘦素串扰在促血管生成分子的增殖、迁移和表达中发挥作用。在本研究中,我们旨在探讨Notch、IL-1和瘦素的抑制对结直肠癌的影响。材料与方法:将指数生长HCT15细胞培养物1 × 107个细胞皮下注射于40只NOD左右后侧腋窝区,制备大肠癌肿瘤异种移植物。CB17-Prkdcscid/J (NOD/SCID)雌性小鼠。然后监测小鼠肿瘤的发展情况,当肿瘤大小达到约150毫米时,将小鼠随机分为五组。小鼠被用来测定γ -分泌酶抑制剂(DAPT, Notch抑制剂),白细胞介素-1受体拮抗剂(Anakinra)和瘦素受体拮抗剂(Allo aca)对肿瘤生长的有效性。治疗结束后,小鼠立即吸入二氧化碳安乐死,并尽一切努力减少痛苦。切除肿瘤进行RT-PCR和组织学分析。结果:存在完整的Notch、IL-1和瘦素信号轴,体内Notch、IL-1和瘦素的拮抗作用影响炎症和血管生成分子的mRNA和蛋白表达。结论:目前的数据表明,靶向Notch、IL-1和瘦素可能具有治疗结直肠癌的潜力。
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来源期刊
CiteScore
4.60
自引率
0.00%
发文量
20
审稿时长
6-12 weeks
期刊介绍: The Turkish Journal of Biology is published electronically 6 times a year by the Scientific and Technological Research Council of Turkey (TÜBİTAK) and accepts English-language manuscripts concerning all kinds of biological processes including biochemistry and biosynthesis, physiology and metabolism, molecular genetics, molecular biology, genomics, proteomics, molecular farming, biotechnology/genetic transformation, nanobiotechnology, bioinformatics and systems biology, cell and developmental biology, stem cell biology, and reproductive biology. Contribution is open to researchers of all nationalities.
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