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甜菜碱通过 PI3K/Akt/mTOR 信号通路对人非小细胞肺癌的潜在化疗作用。

Potential chemotherapeutic effect of betalain against human non-small cell lung cancer through PI3K/Akt/mTOR signaling pathway.

机构信息

Department of Respiratory and Critical Medicine, Central Hospital Affiliated to Shandong First Medical University, Jinan City, China.

Department of Biochemistry, Saveetha Dental College, Saveetha Institute of Medical and Technical Sciences, Saveetha University, Chennai, Tamilnadu, India.

出版信息

Environ Toxicol. 2021 Jun;36(6):1011-1020. doi: 10.1002/tox.23100. Epub 2021 Feb 1.

Abstract

This work focuses on evaluating the therapeutic ability of betalain and its causal mechanisms in NSCLC both in vivo and in vitro. The experimental results demonstrated that betalain was able to reduce the viability of A549 cells dose dependently with undetectable toxicity toward normal human cells. Betalain also augmented the apoptotic cells of A549 and cell cycle arrest which was evidenced via increased in level of p53/p21 and decreasing levels of cyclin-D1 complex. Moreover, betalain also reduced the levels of p-PI3K, p-Akt, and mammalian target of rapamycin significantly, justifying the pro-apoptotic effect on A549 cells. The in vivo anticancer activity of betalain was determined further in nude mice injected with A549 cells. Xenograft in vivo experiments confirmed betalain administration of ameliorates the expression of pro-inflammatory cytokines, tumor markers with reduced toxic effect. Accordingly, this combined study provides significant insight on betalain as a therapeutic agent.

摘要

本研究专注于评估甜菜红素在体内和体外环境下治疗非小细胞肺癌的能力及其作用机制。实验结果表明,甜菜红素能够剂量依赖性地降低 A549 细胞的活力,同时对正常人体细胞几乎没有毒性。甜菜红素还能增加 A549 细胞的凋亡细胞数量并诱导细胞周期停滞,这一作用是通过增加 p53/p21 的水平和降低细胞周期蛋白 D1 复合物的水平来实现的。此外,甜菜红素还能显著降低 p-PI3K、p-Akt 和哺乳动物雷帕霉素靶蛋白的水平,这证明了它对 A549 细胞的促凋亡作用。进一步在接种 A549 细胞的裸鼠中确定了甜菜红素的体内抗癌活性。体内异种移植实验证实,甜菜红素的给药可改善促炎细胞因子和肿瘤标志物的表达,同时降低毒性作用。因此,这项联合研究为甜菜红素作为一种治疗剂提供了重要的见解。

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