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肉桂醛通过抑制 Wnt/β-连环蛋白和 PI3K/Akt 信号通路抑制骨肉瘤的功能。

Cinnamaldehyde Inhibits the Function of Osteosarcoma by Suppressing the Wnt/β-Catenin and PI3K/Akt Signaling Pathways.

机构信息

Department of Orthopedics, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.

Department of Dermatology, The First Affiliated Hospital of Chongqing Medical University, Chongqing 400016, People's Republic of China.

出版信息

Drug Des Devel Ther. 2020 Oct 30;14:4625-4637. doi: 10.2147/DDDT.S277160. eCollection 2020.

DOI:10.2147/DDDT.S277160
PMID:33154629
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7608596/
Abstract

BACKGROUND

Osteosarcoma (OS) is a primary bone tumor associated with locally aggressive growth and early metastatic potential that typically occurs in children and adolescents. Chinese traditional medicine has been shown to have significant tumor-killing effect, in which cinnamaldehyde (CA) is the main active ingredient.

PURPOSE

To explore the anticancer effect of CA on the osteosarcoma cells and the possible molecular mechanism.

METHODS

Crystal violet assay, MTT assay and colony-forming assay were used to confirm the inhibitory role of CA in the proliferation of 143B and MG63 osteosarcoma cells. Hoechst 33258 staining and flow cytometry were used to observe apoptosis. The migration and invasion role of OS cells were evaluated using transwell assays and wound healing assays. Western blotting was used to analyse the protein expression levels. Nude mice were inoculated with 143B cells to establish an orthotopic OS tumor animal model and to investigate the effects of CA on OS tumors.

RESULTS

According to crystal violet assay, MTT assay and colony-forming assay, CA significantly inhibited cell proliferation. Hoechst 33258 staining and flow cytometry analysis showed that CA-induced apoptosis in a concentration-dependent manner. In addition, transwell assays and wound healing assays showed that CA inhibited the migration and invasion of osteosarcoma cells. In vivo mouse models, CA inhibited the growth of osteosarcoma. The potential mechanisms could be that CA inhibited the transcriptional activity of Wnt/β-catenin and PI3K/Akt of the osteosarcoma.

CONCLUSION

CA may inhibit the proliferation, migration, invasion and promote apoptosis of OS cells by inhibiting Wnt/β-catenin and PI3K/Akt signaling pathways. CA may be a potentially effective anti-tumor drug.

摘要

背景

骨肉瘤(OS)是一种与局部侵袭性生长和早期转移潜能相关的原发性骨肿瘤,通常发生在儿童和青少年中。中药已被证明具有显著的肿瘤杀伤作用,其中肉桂醛(CA)是主要的活性成分。

目的

探讨 CA 对骨肉瘤细胞的抗癌作用及其可能的分子机制。

方法

结晶紫法、MTT 法和集落形成实验用于确认 CA 对 143B 和 MG63 骨肉瘤细胞增殖的抑制作用。Hoechst 33258 染色和流式细胞术用于观察细胞凋亡。Transwell 实验和划痕愈合实验用于评估 OS 细胞的迁移和侵袭作用。Western blot 用于分析蛋白表达水平。将 143B 细胞接种于裸鼠建立骨肉瘤原位肿瘤动物模型,探讨 CA 对骨肉瘤肿瘤的作用。

结果

根据结晶紫法、MTT 法和集落形成实验,CA 显著抑制细胞增殖。Hoechst 33258 染色和流式细胞术分析显示,CA 呈浓度依赖性诱导细胞凋亡。此外,Transwell 实验和划痕愈合实验显示 CA 抑制骨肉瘤细胞的迁移和侵袭。体内小鼠模型中,CA 抑制骨肉瘤的生长。潜在机制可能是 CA 通过抑制 Wnt/β-catenin 和 PI3K/Akt 信号通路抑制骨肉瘤的转录活性。

结论

CA 可能通过抑制 Wnt/β-catenin 和 PI3K/Akt 信号通路抑制骨肉瘤细胞的增殖、迁移、侵袭并促进凋亡。CA 可能是一种潜在有效的抗肿瘤药物。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/f12bbc7d07de/DDDT-14-4625-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/74bfe9851dbd/DDDT-14-4625-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/7cdb57c34f2b/DDDT-14-4625-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/65052082154e/DDDT-14-4625-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/8da8dcbdd940/DDDT-14-4625-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/4f6ea4a1b983/DDDT-14-4625-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/f12bbc7d07de/DDDT-14-4625-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/74bfe9851dbd/DDDT-14-4625-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/7cdb57c34f2b/DDDT-14-4625-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/65052082154e/DDDT-14-4625-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/8da8dcbdd940/DDDT-14-4625-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/4f6ea4a1b983/DDDT-14-4625-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/112d/7608596/f12bbc7d07de/DDDT-14-4625-g0006.jpg

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