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萘茜通过B细胞淋巴瘤2/B细胞相关X蛋白信号通路抑制人结肠癌细胞增殖并诱导其凋亡。

Naphthazarin suppresses cell proliferation and induces apoptosis in human colorectal cancer cells via the B-cell lymphoma 2/B-cell associated X protein signaling pathway.

作者信息

Chen Ai-Dong, Li Hui, Li Yong-Chun, Zeng Hai

机构信息

Department of Gastroenterology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.

Department of Medical Oncology, Hongqi Hospital Affiliated to Mudanjiang Medical University, Mudanjiang, Heilongjiang 157011, P.R. China.

出版信息

Oncol Lett. 2016 Dec;12(6):5211-5216. doi: 10.3892/ol.2016.5319. Epub 2016 Oct 26.

Abstract

Colorectal cancer is the most common gastrointestinal cancer in the USA. Naphthazarin, one of the naturally available 1,4-naphthoquinone derivatives, is a natural bioactive molecule that exhibits an antitumor effect. To the best of our knowledge, this is the first study to investigate the anticancer effect of naphthazarin on cell proliferation and apoptosis in human SW480 colorectal cancer cells. In the present study, 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and lactate dehydrogenase assays were performed to assess the effect of napthazarin on cell proliferation and cytotoxicity of SW430 cells, respectively. In addition, an Annexin V-fluorescein isothiocyanate/propidium iodide apoptosis assay and 4',6-diamidino-2-phenylindole staining were used to analyze cell and nuclei apoptosis of SW480 cells, respectively, following treatment with naphthazarin. Poly (ADP-ribose) polymerase (PARP), B-cell lymphoma 2 (Bcl-2) and B-cell associated X protein (Bax) protein expression was analyzed by western blot. Furthermore, caspase-3 activation was analyzed using a commercial kit. The results revealed that naphthazarin exhibited cell growth inhibition, an increase in cytotoxicity and apoptosis induction in SW480 cells, which was associated with activation of the Bax/Bcl-2 signaling pathway and cleaved caspase-3 activation. However, no significant differences in PARP expression were identified following treatment with naphthazarin in SW480 cells. Taken together, these results suggest that naphthazarin decreased cell viability and induced apoptosis of SW480 cells, indicating that naphthazarin may present a potential therapeutic agent for human colorectal cancer treatment.

摘要

结直肠癌是美国最常见的胃肠道癌症。萘茜,一种天然存在的1,4-萘醌衍生物,是一种具有抗肿瘤作用的天然生物活性分子。据我们所知,这是第一项研究萘茜对人SW480结直肠癌细胞增殖和凋亡的抗癌作用的研究。在本研究中,分别进行了3-(4,5-二甲基噻唑-2-基)-2,5-二苯基四氮唑溴盐和乳酸脱氢酶测定,以评估萘茜对SW430细胞增殖和细胞毒性的影响。此外,在用萘茜处理后,分别使用膜联蛋白V-异硫氰酸荧光素/碘化丙啶凋亡测定法和4',6-二脒基-2-苯基吲哚染色法分析SW480细胞的细胞凋亡和细胞核凋亡。通过蛋白质印迹法分析聚(ADP-核糖)聚合酶(PARP)、B细胞淋巴瘤2(Bcl-2)和B细胞相关X蛋白(Bax)的蛋白表达。此外,使用商业试剂盒分析半胱天冬酶-3的激活情况。结果显示,萘茜对SW480细胞具有细胞生长抑制作用,增加细胞毒性并诱导凋亡,这与Bax/Bcl-2信号通路的激活和半胱天冬酶-3的切割激活有关。然而,用萘茜处理SW480细胞后,未发现PARP表达有显著差异。综上所述,这些结果表明萘茜降低了SW480细胞的活力并诱导其凋亡,表明萘茜可能是一种用于人类结直肠癌治疗的潜在治疗剂。

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