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通过 TIGIT-CD155 通路使用阿司匹林预防结直肠癌。

Use of aspirin in the prevention of colorectal cancer through TIGIT-CD155 pathway.

机构信息

Department of Laboratory Medicine, College of Clinical Medicine, Ningxia Medical University, Yinchuan, China.

Department of Oncology Surgery, The First People's Hospital of Yinchuan, Yinchuan, China.

出版信息

J Cell Mol Med. 2019 Jul;23(7):4514-4522. doi: 10.1111/jcmm.14332. Epub 2019 May 14.

Abstract

Colorectal cancer (CRC) is one of the most widespread malignant cancers, with a high incidence and mortality all over the world. Aspirin (ASA) otherwise known as acetylsalicylic acid, is a non-steroidal anti-inflammatory drug that has shown promising results in the prevention of chronic diseases, including several cancers. In previous studies, aspirin has been shown to reduce the incidence of CRC. Immune checkpoint blockade of T cell Ig and ITIM domain receptor (TIGIT) alone or combined with other immune checkpoint blockades moleculars has gained impressive results in the treatment of the melanoma and glioblastoma. Here, we found that TIGIT and Poliovirus receptor (PVR, CD155) are expressed in tumour cells; the TIGIT and CD155 protein expression in cancer tissue has been found to be significantly higher than that in the precancerous tissue. T cell Ig and ITIM domain receptor and CD226 were expressed in the lymphocytes near the tumour tissue and the adjacent tissues. Aspirin has been found to inhibit cancer cell viability and promote CRC cell apoptosis.Similarly, aspirin has also been found to increase pro-apoptotic protein Bax's expression. We found that the expression of TIGIT decreased with an increase in the concentration of aspirin and that the suppression of TIGIT can affect the effect of aspirin on cell proliferation. In this paper, we found that aspirin attenuates cancer cell proliferation and induces CRC cells apoptosis by down-regulating the expression of TIGIT, which provides new evidence for the application of aspirin in cancer treatment.

摘要

结直肠癌(CRC)是最广泛的恶性肿瘤之一,在全球范围内发病率和死亡率都很高。阿司匹林(ASA)又称乙酰水杨酸,是一种非甾体抗炎药,在预防慢性病方面显示出良好的效果,包括几种癌症。以前的研究表明,阿司匹林可以降低 CRC 的发病率。T 细胞免疫球蛋白和 ITIM 结构域受体(TIGIT)的免疫检查点阻断单独或与其他免疫检查点阻断分子联合应用,在治疗黑色素瘤和神经胶质瘤方面取得了令人瞩目的效果。在这里,我们发现 TIGIT 和脊髓灰质炎病毒受体(PVR,CD155)在肿瘤细胞中表达;癌组织中的 TIGIT 和 CD155 蛋白表达明显高于癌前组织。T 细胞免疫球蛋白和 ITIM 结构域受体和 CD226 在肿瘤组织附近的淋巴细胞和相邻组织中表达。我们发现阿司匹林抑制癌细胞活力并促进 CRC 细胞凋亡。同样,阿司匹林也被发现增加促凋亡蛋白 Bax 的表达。我们发现,随着阿司匹林浓度的增加,TIGIT 的表达减少,而抑制 TIGIT 可以影响阿司匹林对细胞增殖的影响。在本文中,我们发现阿司匹林通过下调 TIGIT 的表达来减弱癌细胞的增殖并诱导 CRC 细胞凋亡,为阿司匹林在癌症治疗中的应用提供了新的证据。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/fb8c/6584546/4460690c4a31/JCMM-23-4514-g001.jpg

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