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多炔类化合物通过诱导人肺癌细胞凋亡和改善肺部菌群失调发挥抗癌作用

Polyacetylenes from Root Induced Apoptosis of Human Lung Adenocarcinoma Cells and Improved Lung Dysbiosis.

机构信息

Zhejiang Key Laboratory of Experimental Animal and Safety Evaluation, Zhejiang Academy of Medical Sciences (Hangzhou Medical College), Hangzhou 310013, China.

College of Pharmaceutical Science, Zhejiang Chinese Medical University, Hangzhou 310053, China.

出版信息

Biomed Res Int. 2022 Feb 18;2022:7713355. doi: 10.1155/2022/7713355. eCollection 2022.

Abstract

is a perennial smelly herbaceous plant and widely employed for the treatment of various lung cancer and inflammation. However, the anticancer substances in and their underlying mechanisms had not been well clarified. In this study, six compounds were obtained from the water extracts of polyacetylenes (CLP) and then identified as syringin, codonopilodiynoside A, lobetyol, isolariciresinol, lobetyolin, and atractylenolide III. Treatment with CLP remarkably suppressed the cell proliferation, colony formation, migration, and invasion of A549 cells. Synergistic effects of lobetyolin and lobetyol were equivalent to the antiproliferative activities of CLP, while other compounds did not have any inhibition on the viabilities of A549 cells. CLP also reduced the expression of Ras, PI3K, p-AKT, Bcl-2, cyclin D1, and CDK4 but increased the expression of Bax, GSK-3, clv-caspase-3, and clv-caspase-9, which could be reversed by the PI3K activator 740YP. Furthermore, CLP retarded the growths of tumor and lung pathogenic bacteria in mice. It demonstrated that lobetyolin and lobetyol were the main antitumor compounds in . CLP induced cell apoptosis of lung cancer cells via inactivation of the Ras/PI3K/AKT pathway and ameliorated lung dysbiosis, suggesting the therapeutic potentials for treating human lung cancer.

摘要

是一种多年生有臭味的草本植物,广泛用于治疗各种肺癌和炎症。然而, 中的抗癌物质及其潜在机制尚未得到很好的阐明。在这项研究中,从 的水提取物中获得了六种化合物,然后鉴定为丁香苷、codonopilodiynoside A、lobetyol、异落叶松脂醇、lobetyolin 和 atractylenolide III。CLP 处理显著抑制了 A549 细胞的增殖、集落形成、迁移和侵袭。lobetyolin 和 lobetyol 的协同作用与 CLP 的抗增殖活性相当,而其他化合物对 A549 细胞的活力没有任何抑制作用。CLP 还降低了 Ras、PI3K、p-AKT、Bcl-2、cyclin D1 和 CDK4 的表达,但增加了 Bax、GSK-3、clv-caspase-3 和 clv-caspase-9 的表达,PI3K 激活剂 740YP 可逆转这种作用。此外,CLP 还延缓了小鼠肿瘤和肺部病原菌的生长。结果表明,lobetyolin 和 lobetyol 是 的主要抗癌化合物。CLP 通过失活 Ras/PI3K/AKT 通路诱导肺癌细胞凋亡,并改善肺部菌群失调,提示其在治疗人类肺癌方面的治疗潜力。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/4a08/8881130/33a5e3aaaa42/BMRI2022-7713355.001.jpg

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