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樟芝通过抑制肺癌细胞中的 STAT3 信号通路诱导抗肿瘤活性。

Antrodia cinnamomea induces anti-tumor activity by inhibiting the STAT3 signaling pathway in lung cancer cells.

机构信息

Department of Medical Biotechnology and Laboratory Sciences, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.

Center for Molecular and Clinical Immunology, College of Medicine, Chang Gung University, Taoyuan, 33302, Taiwan.

出版信息

Sci Rep. 2019 Mar 26;9(1):5145. doi: 10.1038/s41598-019-41653-9.

DOI:10.1038/s41598-019-41653-9
PMID:30914735
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6435735/
Abstract

We examined the effects of an Antrodia cinnamomea ethanol extract (ACEE) on lung cancer cells in vitro and tumor growth in vivo. ACEE produced dose-dependent cytotoxic effects and induced apoptosis in Lewis lung carcinoma (LLC) cells. ACEE treatment increased expression of p53 and Bax, as well as cleavage of caspase-3 and PARP, while reducing expression of survivin and Bcl-2. ACEE also reduced the levels of JAK2 and phosphorylated STAT3 in LLC cells. In a murine allograft tumor model, oral administration of ACEE significantly inhibited LLC tumor growth and metastasis without affecting serum biological parameters or body weight. ACEE increased cleavage of caspase-3 in murine tumors, while decreasing STAT3 phosphorylation. In addition, ACEE reduced the growth of human tumor xenografts in nude mice. Our findings therefore indicate that ACEE inhibits lung tumor growth and metastasis by inducing apoptosis and by inhibiting the STAT3 signaling pathway in cancer cells.

摘要

我们研究了樟芝乙醇提取物(ACEE)对肺癌细胞的体外作用和体内肿瘤生长的影响。ACEE 产生了剂量依赖性的细胞毒性作用,并诱导了 Lewis 肺癌(LLC)细胞的凋亡。ACEE 处理增加了 p53 和 Bax 的表达,同时也促进了 caspase-3 和 PARP 的切割,而降低了 survivin 和 Bcl-2 的表达。ACEE 还降低了 LLC 细胞中 JAK2 和磷酸化 STAT3 的水平。在小鼠同种异体移植肿瘤模型中,口服 ACEE 显著抑制了 LLC 肿瘤的生长和转移,而不影响血清生物学参数或体重。ACEE 增加了小鼠肿瘤中 caspase-3 的切割,同时降低了 STAT3 的磷酸化。此外,ACEE 减少了裸鼠中人类肿瘤异种移植物的生长。因此,我们的研究结果表明,ACEE 通过诱导细胞凋亡和抑制癌细胞中的 STAT3 信号通路来抑制肺肿瘤的生长和转移。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/b43f3e9744eb/41598_2019_41653_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/319357787b80/41598_2019_41653_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/ce4d954bd0ec/41598_2019_41653_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/0d66b2638783/41598_2019_41653_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/8fcff238e167/41598_2019_41653_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/066b7289945b/41598_2019_41653_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/b43f3e9744eb/41598_2019_41653_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/319357787b80/41598_2019_41653_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/ce4d954bd0ec/41598_2019_41653_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/0d66b2638783/41598_2019_41653_Fig3_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/8fcff238e167/41598_2019_41653_Fig4_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/066b7289945b/41598_2019_41653_Fig5_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/e2d3/6435735/b43f3e9744eb/41598_2019_41653_Fig6_HTML.jpg

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