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通过诱导G2/M期细胞周期阻滞和凋亡实现的硒形态依赖性癌症放射增敏作用。

Selenium speciation-dependent cancer radiosensitization by induction of G2/M cell cycle arrest and apoptosis.

作者信息

Nie Shiqing, He Xin, Sun Zhiting, Zhang Yan, Liu Ting, Chen Tianfeng, Zhao Jianfu

机构信息

Department of Oncology of the First Affiliated Hospital, Jinan University, Guangzhou, Guangdong, China.

出版信息

Front Bioeng Biotechnol. 2023 Mar 22;11:1168827. doi: 10.3389/fbioe.2023.1168827. eCollection 2023.

Abstract

Radiation therapy has Q6long been a routine and effective treatment for non-small cell lung cancer (NSCLC), but the radioresistance and side effects have limited its application. In recent years, the superiority showed by trace element selenium in tumor radiotherapy sensitization has received wide attention. However, different forms of selenium compounds exhibit different chemical properties and their mechanisms of action on tumors may be different. Human non-small cell lung cancer SPC-A1 cells were studied. Drug toxicity was detected by MTT assay. The selenium content absorbed in vitro at different time points was detected by ICP-MS. Colony formation were conducted to observe the radiosensitization effect of different selenium compounds on SPC-A1 cells, and to compare the proliferation ability of SPC-A1 cells treated by radiation alone and radiation combined with different selenium compounds. Cell migration was detected by cell scratch assay. The changes of cell cycle and apoptosis were detected by flow cytometry. DCFH-DA fluorescent probe was used to detect the effects of different selenium compounds combined with X-ray on ROS production. In this study, these four representative selenium compounds all have a certain ability to enhance the ability of radiotherapy to inhibit tumor cell proliferation and migration, and the mechanism may be related to blocking cell cycle in G2/M phase, activating the caspase cascade and reducing intracellular ROS levels to induce tumor cell apoptosis. Among them, -2-valent organic selenium has the most obvious effect, mainly inhibits cell migration, and induces early apoptosis by activating a large number of caspase-3, and arrest the cell cycle in S phase and G2/M phase. 0-valent selenium nanoparticles mainly arrest the cell cycle in G2/M phase. +4-valent inorganic selenium exerts its antitumor effects primarily by inhibiting tumor cell migration and inducing early apoptosis of tumor cells. In this paper, the antitumor effects of four different forms of selenium compounds combined with X-rays on SPC-A1 cells were investigated, and their inhibitory effects on the proliferation and migration of cancer cells and their mechanisms were examined. We found that the radiosensitizing effect of selenium on NSCLC was closely related to its selenium form through the study of the sensitizing effect of different kinds of selenium compounds on radiotherapy.

摘要

放射治疗长期以来一直是治疗非小细胞肺癌(NSCLC)的常规且有效方法,但放射抗性和副作用限制了其应用。近年来,微量元素硒在肿瘤放射增敏方面表现出的优势受到广泛关注。然而,不同形式的硒化合物具有不同的化学性质,它们对肿瘤的作用机制可能也不同。本研究以人非小细胞肺癌SPC-A1细胞为研究对象。采用MTT法检测药物毒性。用ICP-MS检测不同时间点体外吸收的硒含量。进行集落形成实验以观察不同硒化合物对SPC-A1细胞的放射增敏作用,并比较单独放疗及放疗联合不同硒化合物处理后SPC-A1细胞的增殖能力。采用细胞划痕实验检测细胞迁移情况。通过流式细胞术检测细胞周期和凋亡的变化。用DCFH-DA荧光探针检测不同硒化合物联合X射线对活性氧(ROS)产生的影响。在本研究中,这四种代表性的硒化合物均具有一定增强放疗抑制肿瘤细胞增殖和迁移能力的作用,其机制可能与阻断细胞周期于G2/M期、激活半胱天冬酶级联反应以及降低细胞内ROS水平以诱导肿瘤细胞凋亡有关。其中,-2价有机硒作用最为明显,主要抑制细胞迁移,通过激活大量半胱天冬酶-3诱导早期凋亡,并使细胞周期阻滞于S期和G2/M期。0价硒纳米颗粒主要使细胞周期阻滞于G2/M期。+4价无机硒主要通过抑制肿瘤细胞迁移和诱导肿瘤细胞早期凋亡发挥其抗肿瘤作用。本文研究了四种不同形式的硒化合物联合X射线对SPC-A1细胞的抗肿瘤作用,考察了它们对癌细胞增殖和迁移的抑制作用及其机制。通过研究不同种类硒化合物对放疗的增敏作用,我们发现硒对NSCLC的放射增敏作用与其硒的形态密切相关。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/7f6f/10073679/eb9ee126dad3/fbioe-11-1168827-g001.jpg

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