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臭椿酮通过下调RPA1抑制DNA复制来抑制非小细胞肺癌细胞的生长。

Ailanthone inhibits non-small cell lung cancer cell growth through repressing DNA replication via downregulating RPA1.

作者信息

Ni Zhongya, Yao Chao, Zhu Xiaowen, Gong Chenyuan, Xu Zihang, Wang Lixin, Li Suyun, Zou Chunpu, Zhu Shiguo

机构信息

Laboratory of Integrative Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd, Shanghai 201203, PR China.

Department of Internal Classic of Medicine, School of Basic Medical Sciences, Shanghai University of Traditional Chinese Medicine, 1200 Cai Lun Rd, Shanghai 201203, PR China.

出版信息

Br J Cancer. 2017 Nov 21;117(11):1621-1630. doi: 10.1038/bjc.2017.319. Epub 2017 Oct 12.

DOI:10.1038/bjc.2017.319
PMID:29024939
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5729430/
Abstract

BACKGROUND

The identification of bioactive compounds from Chinese medicine plays a crucial role in the development of novel reagents against non-small lung cancer (NSCLC).

METHODS

High throughput screening assay and analyses of cell growth, cell cycle, apoptosis, cDNA microarray, BrdU incorporation and gene expression were performed.

RESULTS

Ailanthone (Aila) suppressed NSCLC cell growth and colony formation in vitro and inhibited NSCLC tumour growth in subcutaneously xenografted and orthotopic lung tumour models, leading to prolonged survival of tumour-bearing mice. Moreover, Aila induced cell cycle arrest in a dose-independent manner but did not induce apoptosis in all NSCLC cells. Furthermore, 1222 genes were differentially expressed upon Aila administration, which were involved in 21 signal pathways, such as DNA replication. In addition, Aila dose-dependently decreased BrdU incorporation and downregulated the expression of replication protein A1 (RPA1).

CONCLUSIONS

Aila inhibited the growth of NSCLC cells through the repression of DNA replication via downregulating RPA1, rather than through cell cycle arrest and apoptosis. Our findings suggested that Aila could be used as a promising therapeutic candidate for NSCLC patients.

摘要

背景

从中药中鉴定生物活性化合物在开发抗非小细胞肺癌（NSCLC）的新型试剂中起着关键作用。

方法

进行了高通量筛选试验以及细胞生长、细胞周期、细胞凋亡、cDNA微阵列、BrdU掺入和基因表达分析。

结果

臭椿酮（Aila）在体外抑制NSCLC细胞生长和集落形成，并在皮下异种移植和原位肺肿瘤模型中抑制NSCLC肿瘤生长，导致荷瘤小鼠生存期延长。此外，Aila以剂量非依赖性方式诱导细胞周期停滞，但并非在所有NSCLC细胞中都诱导凋亡。此外，给予Aila后有1222个基因差异表达，这些基因涉及21条信号通路，如DNA复制。另外，Aila剂量依赖性地降低BrdU掺入并下调复制蛋白A1（RPA1）的表达。

结论

Aila通过下调RPA1抑制DNA复制，而非通过细胞周期停滞和凋亡来抑制NSCLC细胞的生长。我们的研究结果表明，Aila可作为NSCLC患者有前景的治疗候选药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/f9d0ca91ed6b/bjc2017319f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/afd78744ae08/bjc2017319f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/f5c71df3d9e3/bjc2017319f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/4a3ce19d8640/bjc2017319f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/2f256d979fb8/bjc2017319f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/d0e790225ec9/bjc2017319f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/f9d0ca91ed6b/bjc2017319f6.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/afd78744ae08/bjc2017319f1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/f5c71df3d9e3/bjc2017319f2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/4a3ce19d8640/bjc2017319f3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/2f256d979fb8/bjc2017319f4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/d0e790225ec9/bjc2017319f5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/93ce/5729430/f9d0ca91ed6b/bjc2017319f6.jpg

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