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提示1 过表达抑制人骨肉瘤细胞的细胞周期并诱导其细胞凋亡。

Hint1 Overexpression Inhibits the Cell Cycle and Induces Cell Apoptosis in Human Osteosarcoma Cells.

作者信息

Duan Dong-Dong, Xie Hui, Shi Hua-Feng, Huang Wen-Wen, Ding Fan, Hong Jia-Kun, Fan Jun-Sheng, Hu Shou-Yong, Wang Qing-Wei, Zhou Meng-Qiao

机构信息

Department of Orthopedic Surgery, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, People's Republic of China.

Department of Cardiology, The First People's Hospital of Jingmen, Jingmen, Hubei 448000, People's Republic of China.

出版信息

Onco Targets Ther. 2020 Aug 19;13:8223-8232. doi: 10.2147/OTT.S242344. eCollection 2020.

DOI:10.2147/OTT.S242344
PMID:32884300
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7443417/
Abstract

BACKGROUND

New evidence suggests that histidine triad nucleotide-binding protein 1 (Hint1) exerts a tumor suppressor effect in various human tumors, such as colorectal cancer and gastric cancer. However, it has not been reported whether Hint1 is involved in the occurrence and development of osteosarcoma (OS).

MATERIALS AND METHODS

The present study investigated the role of Hint1 in human OS cells by using cell lines, including 143B, U2OS, KHOS-240S, Saos-2 and MG-63. Cell proliferation and apoptosis were detected by flow cytometry.

RESULTS

The present result revealed that Hint1 is downregulated in these cell lines. The overexpression of Hint1 by adenovirus transfection in 143B and MG63 cell lines suppressed the proliferation and cell cycle, and increased the cell apoptosis. Mechanically, it was found that Hint1 downregulated the cyclin D1 expression via FOXO1 inhibition. Furthermore, FOXO1 overexpression in the 143B and MG63 cell lines significantly blurred the effects of Hint1 on cellular proliferation and apoptosis.

CONCLUSION

The present study indicates that Hint1 inhibits the development of OS by regulating FoxO1-cyclin D1, suggesting that Hint1 may be a new method for the treatment of OS.

摘要

背景

新证据表明，组氨酸三联体核苷酸结合蛋白1（Hint1）在多种人类肿瘤中发挥肿瘤抑制作用，如结直肠癌和胃癌。然而，尚未有关于Hint1是否参与骨肉瘤（OS）发生发展的报道。

材料与方法

本研究通过使用包括143B、U2OS、KHOS - 240S、Saos - 2和MG - 63在内的细胞系，研究Hint1在人OS细胞中的作用。通过流式细胞术检测细胞增殖和凋亡。

结果

本研究结果显示，这些细胞系中Hint1表达下调。通过腺病毒转染在143B和MG63细胞系中过表达Hint1可抑制细胞增殖和细胞周期，并增加细胞凋亡。机制上，发现Hint1通过抑制FOXO1下调细胞周期蛋白D1的表达。此外，在143B和MG63细胞系中过表达FOXO1显著削弱了Hint1对细胞增殖和凋亡的影响。

结论

本研究表明，Hint1通过调节FoxO1 - 细胞周期蛋白D1抑制OS的发展，提示Hint1可能是治疗OS的一种新方法。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/937ea3efa7b6/OTT-13-8223-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/f8039b938351/OTT-13-8223-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/cf5f96abb17d/OTT-13-8223-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/781ff4f72385/OTT-13-8223-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/2c4d25ef348b/OTT-13-8223-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/08fe3b6abd3c/OTT-13-8223-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/937ea3efa7b6/OTT-13-8223-g0006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/f8039b938351/OTT-13-8223-g0001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/cf5f96abb17d/OTT-13-8223-g0002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/781ff4f72385/OTT-13-8223-g0003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/2c4d25ef348b/OTT-13-8223-g0004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/08fe3b6abd3c/OTT-13-8223-g0005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/19cf/7443417/937ea3efa7b6/OTT-13-8223-g0006.jpg

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