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研究茄科植物治疗结肠癌的分子机制。

Study on the molecular mechanism of nightshade in the treatment of colon cancer.

机构信息

Department of Oncology, Chongqing Traditional Chinese Medicine Hospital, Chongqing, 400020, China.

Department of Nephrology, Chongqing Hospital Of Traditional Chinese Medicine, Chongqing, 400020 China.

出版信息

Bioengineered. 2022 Jan;13(1):1575-1589. doi: 10.1080/21655979.2021.2016045.

DOI:10.1080/21655979.2021.2016045
PMID:35012428
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8805967/
Abstract

The present study attempts to explore the effective components, action targets, and potential mechanism of nightshade for colon cancer treatment. The relationship network diagram of 'traditional Chinese medicine - component - target - disease' was firstly constructed by employing network pharmacology. Experiments were conducted in vivo and in vitro to verify the influence of quercetin, the core effective component of nightshade, on colon cancer. Meanwhile, the regulatory effects of quercetin on core targets and main signaling pathways were determined. Based on the network diagram of 'traditional Chinese medicine - component - target - disease' and KEGG analysis, quercetin might exhibit certain effects on colon cancer treatment by regulating the biological behavior of core targets related to cell apoptosis in tumors including PIK3R1, PIK3CA, Akt1, and Akt2. Furthermore, quercetin has been demonstrated in vitro experiments to suppress the proliferation and migration of colon cancer cells whereas promote their apoptosis in a dose-dependent fashion. In vivo experiments indicate that quercetin had an antitumor effect on human colon cancer SW480 cells in nude mice bearing tumors. Furthermore, PIK3CA could bind to quercetin directly, which is validated by immunocoprecipitation. Therefore, the activation of PI3K/AKT phosphorylation was inhibited by quercetin and moreover the expressions of apoptotic proteins caspase-3 and Bcl2-Associated X protein (BAX) were up-regulated. In conclusion, the potential mechanism of nightshade lies in the activation of the PI3K/AKT signaling pathway inhibited by quercetin, thus promoting apoptosis of colon cancer cells for colon cancer treatment.

摘要

本研究旨在探索茄科植物治疗结肠癌的有效成分、作用靶点及潜在机制。首先采用网络药理学构建“中药-成分-靶点-疾病”关系网络图，然后通过体内和体外实验验证茄科植物中核心有效成分槲皮素对结肠癌的影响，同时确定槲皮素对核心靶点和主要信号通路的调控作用。基于“中药-成分-靶点-疾病”网络图和 KEGG 分析，槲皮素可能通过调节与肿瘤细胞凋亡相关的核心靶点的生物学行为对结肠癌治疗产生一定的影响，这些核心靶点包括 PIK3R1、PIK3CA、Akt1 和 Akt2。此外，体外实验表明槲皮素能够以剂量依赖的方式抑制结肠癌细胞的增殖和迁移，促进其凋亡。体内实验表明，槲皮素对荷瘤裸鼠人结肠癌 SW480 细胞具有抗肿瘤作用。进一步通过免疫共沉淀实验验证了 PIK3CA 可以与槲皮素直接结合，从而抑制 PI3K/AKT 磷酸化的激活，上调凋亡蛋白 caspase-3 和 Bcl2 相关 X 蛋白（BAX）的表达。综上所述，茄科植物治疗结肠癌的潜在机制可能在于槲皮素抑制 PI3K/AKT 信号通路的激活，从而促进结肠癌细胞的凋亡。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/db2dc15d594c/KBIE_A_2016045_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/5d146b43f345/KBIE_A_2016045_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/969aa45e30a2/KBIE_A_2016045_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/e504ec52b0a4/KBIE_A_2016045_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/83ac3b5139a6/KBIE_A_2016045_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/a38b2324a7db/KBIE_A_2016045_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/244ee48dfbc2/KBIE_A_2016045_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/db2dc15d594c/KBIE_A_2016045_F0006_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/5d146b43f345/KBIE_A_2016045_UF0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/969aa45e30a2/KBIE_A_2016045_F0001_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/e504ec52b0a4/KBIE_A_2016045_F0002_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/83ac3b5139a6/KBIE_A_2016045_F0003_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/a38b2324a7db/KBIE_A_2016045_F0004_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/244ee48dfbc2/KBIE_A_2016045_F0005_OC.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a13b/8805967/db2dc15d594c/KBIE_A_2016045_F0006_OC.jpg

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