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磷酸肌醇3激酶的靶向抑制会损害结肠癌中的细胞增殖、存活和侵袭。

Targeted inhibition of the phosphoinositide 3-kinase impairs cell proliferation, survival, and invasion in colon cancer.

作者信息

Yang Fei, Gao Jun-Yi, Chen Hua, Du Zhen-Hua, Zhang Xue-Qun, Gao Wei

机构信息

Department of Pathology, Jinan Central Hospital Affiliated to Shandong University, Jinan.

Department of Clinical Medicine, Weifang Medical College, Weifang.

出版信息

Onco Targets Ther. 2017 Sep 11;10:4413-4422. doi: 10.2147/OTT.S145601. eCollection 2017.

DOI:10.2147/OTT.S145601
PMID:28979133
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC5602681/
Abstract

BACKGROUND

Colon cancer is the third most common cancer in the world, and its metastasis and drug resistance are challenging for its effective treatment. The PI3K/Akt/mTOR pathway plays a crucial role in the pathogenesis of colon cancer. The aim of this study was to investigate the targeting of PI3K in colon cancer cells HT-29 and HCT-116 in vitro.

METHODS

In HT-29 and HCT-116 cells, BEZ235, a dual inhibitor of PI3K/mTOR, and shRNAtarget to PI3KCA were used to inhibit PI3K/Akt/mTOR pathway. The inhibition efficiency of PI3K/Akt/mTOR pathway was detected by RT-PCR and Western blot. Cell proliferation, migration, invasion, and apoptosis were evaluated by Cell Counting Kit-8, Transwell, and flow cytometry assays. The expression of apoptosis-related proteins (cleavage caspase 3, Bcl-2, Bax, and Bim) were also detected.

RESULTS

We found that in HT-29 and HCT-116 cells, the treatment of BEZ235 (1 μM) and PI3KCA knockdown inhibited the activation of PI3K/Akt/mTOR pathway and significantly suppressed cell proliferation, migration, and invasion of HT-29 and HCT-116 cells. In addition, we confirmed that knockdown of BEZ235 and PI3KCA induced cell apoptosis through the upregulated levels of cleavage caspase 3 and Bax and downregulated expression of Bcl-2 and Bim.

CONCLUSION

Our results indicated that targeted inhibition of the PI3K/Akt/mTOR pathway impaired cell proliferation, survival, and invasion in human colon cancer.

摘要

背景

结肠癌是全球第三大常见癌症，其转移和耐药性对有效治疗构成挑战。PI3K/Akt/mTOR通路在结肠癌的发病机制中起关键作用。本研究旨在体外研究PI3K在结肠癌细胞HT - 29和HCT - 116中的靶向作用。

方法

在HT - 29和HCT - 116细胞中，使用PI3K/mTOR双重抑制剂BEZ235和针对PI3KCA的短发夹RNA（shRNA）来抑制PI3K/Akt/mTOR通路。通过RT - PCR和蛋白质免疫印迹法检测PI3K/Akt/mTOR通路的抑制效率。通过细胞计数试剂盒 - 8、Transwell实验和流式细胞术检测细胞增殖、迁移、侵袭和凋亡情况。还检测了凋亡相关蛋白（裂解的半胱天冬酶3、Bcl - 2、Bax和Bim）的表达。

结果

我们发现，在HT - 29和HCT - 116细胞中，用BEZ235（1μM）处理和敲低PI3KCA可抑制PI3K/Akt/mTOR通路的激活，并显著抑制HT - 29和HCT - 116细胞的增殖、迁移和侵袭。此外，我们证实敲低BEZ235和PI3KCA可通过上调裂解的半胱天冬酶3和Bax的水平以及下调Bcl - 2和Bim的表达诱导细胞凋亡。

结论

我们的结果表明，靶向抑制PI3K/Akt/mTOR通路会损害人结肠癌细胞的增殖、存活和侵袭。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/a101f221e363/ott-10-4413Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/075ebb9f2a22/ott-10-4413Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/997d405b7c34/ott-10-4413Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/d0745b65bceb/ott-10-4413Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/a101f221e363/ott-10-4413Fig4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/075ebb9f2a22/ott-10-4413Fig1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/997d405b7c34/ott-10-4413Fig2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/d0745b65bceb/ott-10-4413Fig3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d964/5602681/a101f221e363/ott-10-4413Fig4.jpg

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1
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Int J Nanomedicine. 2016 May 5;11:1947-58. doi: 10.2147/IJN.S100744. eCollection 2016.
2
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3
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Cancers (Basel). 2022 Nov 29;14(23):5894. doi: 10.3390/cancers14235894.
4
Survival of HT29 cancer cells is influenced by hepatocyte growth factor receptor inhibition through modulation of self-DNA-triggered TLR9-dependent autophagy response.肝细胞生长因子受体抑制通过调节自身 DNA 触发的 TLR9 依赖性自噬反应影响 HT29 癌细胞的存活。
PLoS One. 2022 May 12;17(5):e0268217. doi: 10.1371/journal.pone.0268217. eCollection 2022.
5
Withholding of M-CSF Supplement Reprograms Macrophages to M2-Like via Endogenous Activation.抑制 M-CSF 补充剂通过内源性激活将巨噬细胞重编程为 M2 样细胞。
Int J Mol Sci. 2021 Mar 29;22(7):3532. doi: 10.3390/ijms22073532.
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4
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5
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8
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