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在体、内外研究石蒜凝集素诱导人肺腺癌细胞 A549 凋亡和 G2/M 细胞周期阻滞的分子机制。

Molecular mechanisms of Lycoris aurea agglutinin-induced apoptosis and G2 /M cell cycle arrest in human lung adenocarcinoma A549 cells, both in vitro and in vivo.

机构信息

School of Life Sciences & Key Laboratory of Bio-resources, Ministry of Education, Sichuan University, Chengdu 610064, China.

出版信息

Cell Prolif. 2013 Jun;46(3):272-82. doi: 10.1111/cpr.12034.

DOI:10.1111/cpr.12034
PMID:23692086
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6495545/
Abstract

OBJECTIVES

Lycoris is aurea agglutinin (LAA) has attracted rising attention due to its remarkable bioactivities. Here, we aimed at investigating its anti-tumor activities.

MATERIAL AND METHODS

In vitro methods including MTT, cellular morphology observation, FCM and immunoblotting were performed. In vivo methods like detection of tumor volume, body weight and survival ratio, as well as TUNEL staining were performed.

RESULTS AND CONCLUSION

LAA triggers G2 /M phase cell cycle arrest via up-regulating p21expression as well as down-regulating cdk-1cyclinA singling pathway, and induces apoptotic cell death through inhibiting PI3K-Akt survival pathway in human lung adenocarcinoma A549 cells. While LAA has no significant cytotoxic effect toward normal human embryonic lung fibroblast HELF cells, and moreover, LAA could amplify the antineoplastic effects of cisplatin toward A549 cells. Lastly LAA also bears anti-cancer and apoptosis-inducing effects in vivo, and it could decrease the volume and weight of subcutaneous tumor mass obviously as well as expand lifespan of mice. These findings may provide a new perspective for elucidating the complicated molecular mechanisms of LAA-induced cancer cell growth-inhibition and death, providing a new opportunity of LAA as a potential candidate anti-neoplastic drug for future cancer therapeutics.

摘要

目的

石蒜凝集素(LAA)因具有显著的生物活性而受到越来越多的关注。本研究旨在探讨其抗肿瘤活性。

材料和方法

采用 MTT、细胞形态观察、FCM 和免疫印迹等体外方法,以及检测肿瘤体积、体重和存活率以及 TUNEL 染色等体内方法。

结果和结论

LAA 通过上调 p21 表达和下调 cdk-1/cyclinA 信号通路,诱导人肺腺癌细胞 A549 发生 G2/M 期细胞周期阻滞,并通过抑制 PI3K-Akt 存活途径诱导细胞凋亡。虽然 LAA 对正常人类胚胎肺成纤维细胞 HELF 细胞没有明显的细胞毒性作用,但 LAA 可以增强顺铂对 A549 细胞的抗肿瘤作用。最后,LAA 还具有体内抗癌和诱导细胞凋亡的作用,可明显降低皮下肿瘤体积和重量,延长小鼠的寿命。这些发现可能为阐明 LAA 诱导癌细胞生长抑制和死亡的复杂分子机制提供新的视角,并为 LAA 作为未来癌症治疗的潜在抗肿瘤药物提供新的机会。