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基于对 CTSB 基因的响应,探讨三七总皂苷治疗肺癌的作用机制。

Mechanism of action of Panax notoginoside against lung cancer in mice based on response to CTSB gene.

机构信息

Department of Oncology, Wenzhou Hospital of Traditional Chinese Medicine Affiliated to Zhejiang Chinese Medicine University, Wenzhou, China.

Nanjing University of Chinese Medicine, Nanjing, China.

出版信息

BMC Complement Med Ther. 2020 Nov 25;20(1):367. doi: 10.1186/s12906-020-03159-0.

DOI:10.1186/s12906-020-03159-0
PMID:33238959
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7691060/
Abstract

BACKGROUND

This study aimed to investigate the mechanism of action of Panax notoginoside (PNS) against lung cancer and inhibition of lung cancer cell proliferation by the drug at different concentrations in a mouse model, considering the cathepsin B (CTSB) gene as a target.

METHODS

The mice were randomly assigned into the following five groups: normal control, tumor-bearing, low-dose Panax notoginoside (TSPN), medium-dose TSPN, and high-dose TSPN. All mice were treated with physiological saline or TSPN at different concentrations for 28 days consecutively by gavage. The tumor size was measured, the tumor growth was observed, and the survival curve was drawn. At different time points, the expression of the CTSB gene was detected using quantitative fluorescent polymerase chain reaction, Western blot analysis, and indirect immunofluorescence. The serum indices, such as carcinoembryonic antigen (CEA), neuron-specific enolase (NSE), and Soluble fragment of cytokeratin 19 (CYFRA21), were detected by enzyme-linked immunosorbent assay.

RESULTS

In vivo, PNS could directly inhibit the expression of the CTSB gene in tumors of mice, limit tumor growth, and alter tumor-related indices, such as CEA, NSE, and CYFRA21 levels, in the serum to different extents simultaneously.

CONCLUSION

CTSB gene was closely related to the pathogenesis of lung cancer. PNS could act on the CTSB gene, downregulate the expression of CTSB in lung cancer cells, inhibit the proliferation and invasion of tumors, and prolong the survival period.

摘要

背景

本研究旨在探讨三七总皂苷(PNS)通过作用于组织蛋白酶 B(CTSB)基因抑制肺癌细胞增殖的作用机制,并观察不同浓度的三七总皂苷在肺癌小鼠模型中的抑瘤作用。

方法

将小鼠随机分为正常对照组、荷瘤组、低剂量三七总皂苷(TSPN)组、中剂量 TSPN 组、高剂量 TSPN 组,每组 10 只。除正常对照组外,其余各组小鼠均采用皮下注射接种人肺癌 A549 细胞悬液的方法构建肺癌模型。建模成功后,各组小鼠分别给予生理盐水或不同浓度的 TSPN 连续灌胃 28 d。观察各组小鼠肿瘤生长情况,测量肿瘤体积,绘制生存曲线;采用实时荧光定量聚合酶链反应、Western blot 及间接免疫荧光法检测不同时间点各组小鼠肿瘤组织中 CTSB 基因的表达情况;酶联免疫吸附试验检测各组小鼠血清中癌胚抗原(CEA)、神经元特异性烯醇化酶(NSE)、细胞角蛋白 19 可溶性片段(CYFRA21)等肿瘤标志物的水平。

结果

体内实验结果显示,PNS 可直接抑制小鼠肿瘤组织中 CTSB 基因的表达,不同程度地抑制肿瘤生长,改变血清中与肿瘤相关的标志物 CEA、NSE、CYFRA21 等水平。

结论

CTSB 基因与肺癌的发生发展密切相关。PNS 可能通过作用于 CTSB 基因,下调肺癌细胞中 CTSB 的表达,抑制肿瘤的增殖和侵袭,从而延长荷瘤小鼠的生存期。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/a0edc1760ec4/12906_2020_3159_Fig10_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/eb10e2d6feee/12906_2020_3159_Fig1_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/21149efea872/12906_2020_3159_Fig2_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/3f87a912341e/12906_2020_3159_Fig3_HTML.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/d4ee32aca8f3/12906_2020_3159_Fig6_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/cd6340db27f1/12906_2020_3159_Fig7_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/bccbc1066bb8/12906_2020_3159_Fig8_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/39633d97a7ae/12906_2020_3159_Fig9_HTML.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/b61e/7691060/a0edc1760ec4/12906_2020_3159_Fig10_HTML.jpg

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