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Analgesic-antitumor peptide induces apoptosis and inhibits the proliferation of SW480 human colon cancer cells

机译:镇痛抗肿瘤肽诱导细胞凋亡并抑制SW480人结肠癌细胞的增殖

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摘要

Colorectal cancer is one of the most common malignant tumors, and is associated with significant morbidity and mortality. In this study, recombinant analgesic-antitumor peptide (rAGAP), a protein consisting of small ubiquitin-related modifier (SUMO) linked with a hexa-histidine tag, was used as an antitumor analgesic peptide. The purpose of the present study was to investigate the antitumor activity of rAGAP in human colon adenocarcinoma SW480 cells and its potential molecular mechanisms of action. In this study, cell viability and apoptosis of rAGAP-treated SW480 cells was evaluated by the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay, flow cytometry and 4′,6-diamidino-2-phenylindole (DAPI) staining. Western blotting was used to investigate the effects of rAGAP on p27, Bcl-2/Bax and PTEN/PI3K/Akt cellular signal transduction. Our results showed that rAGAP not only enhanced apoptosis, but also inhibited the proliferation of SW480 cells. rAGAP upregulates the expression of p27 in SW480 cells and leads to cell cycle arrest in the G1 phase. Furthermore, rAGAP significantly increases the production of Bax and PTEN and suppresses the activation of Bcl-2, phosphatidylinositol 3-kinase (PI3K) and phospho-Akt (p-Akt) in SW480 cells. These results suggest that rAGAP may be a potential new anti-colorectal cancer drug.
机译:大肠癌是最常见的恶性肿瘤之一,并与明显的发病率和死亡率相关。在这项研究中,重组止痛抗肿瘤肽(rAGAP)是由与六组氨酸标签相连的泛素相关修饰剂(SUMO)组成的蛋白质,被用作抗肿瘤止痛肽。本研究的目的是研究rAGAP在人结肠腺癌SW480细胞中的抗肿瘤活性及其潜在的分子作用机理。在这项研究中,通过3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四溴甲烷(MTT)测定,流式细胞术和4',6评价了rAGAP处理的SW480细胞的细胞活力和凋亡。 -二mid基-2-苯基吲哚(DAPI)染色。 Western印迹用于研究rAGAP对p27,Bcl-2 / Bax和PTEN / PI3K / Akt细胞信号转导的影响。我们的结果表明,rAGAP不仅可以增强细胞凋亡,而且可以抑制SW480细胞的增殖。 rAGAP上调SW480细胞中p27的表达,并导致细胞周期停滞在G1期。此外,rAGAP可显着增加Bax和PTEN的产生,并抑制SW480细胞中Bcl-2,磷脂酰肌醇3-激酶(PI3K)和磷酸化Akt(p-Akt)的激活。这些结果表明,rAGAP可能是潜在的抗结直肠癌新药。

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