Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma

Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Wang Zhuangqiang, Cui Xiaopeng, Hao Gaopeng, He Jiefeng
Formato:	article
Lenguaje:	EN
Publicado:	De Gruyter 2021
Materias:	caspases cell death liver cancer pi3k/akt signaling pten Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/fa72f5e1f7ad49be96fc44c925352846
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fa72f5e1f7ad49be96fc44c925352846
record_format	dspace
spelling	oai:doaj.org-article:fa72f5e1f7ad49be96fc44c9253528462021-12-05T14:10:41ZAberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma2391-541210.1515/biol-2021-0101https://doaj.org/article/fa72f5e1f7ad49be96fc44c9253528462021-09-01T00:00:00Zhttps://doi.org/10.1515/biol-2021-0101https://doaj.org/toc/2391-5412Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.Wang ZhuangqiangCui XiaopengHao GaopengHe JiefengDe Gruyterarticlecaspasescell deathliver cancerpi3k/akt signalingptenBiology (General)QH301-705.5ENOpen Life Sciences, Vol 16, Iss 1, Pp 1037-1044 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	caspases cell death liver cancer pi3k/akt signaling pten Biology (General) QH301-705.5
spellingShingle	caspases cell death liver cancer pi3k/akt signaling pten Biology (General) QH301-705.5 Wang Zhuangqiang Cui Xiaopeng Hao Gaopeng He Jiefeng Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
description	Phosphatidylinositol 3-kinase (PI3K)/AKT signaling is a crucial pathway for cell survival and proliferation, which are regulated by several growth factors and activated receptors. Upregulated PI3K/AKT signaling molecules were reported in several cancers and they are associated with altered cellular functions, leading to oncogenesis. Here, we have examined the implications of elevated PI3K/AKT expression in the apoptosis resistance of human hepatocellular carcinoma (HCC) Huh7 cells. We showed that PI3K/AKT signaling is significantly upregulated in Huh7 cells by quantitative polymerase chain reaction and protein expression analysis. Also, perversely upregulated PI3K/AKT signaling Huh7 cells are highly resistant to treatment with chemotherapy drugs (docetaxel and sorafenib) and acquired apoptosis resistance through downregulation of tumor suppressor protein PTEN (phosphatase and tensin homolog deleted on chromosome ten). Hence, we have investigated the effect of PTEN overexpression on apoptosis induction in Huh7 cells. We showed that PTEN overexpressed Huh7 cells became more sensitive toward the aforesaid drugs and induced apoptotic cell death due to intracellular reactive oxygen species (ROS) generation. Concurrently, the overexpression of PTEN leads to the activation of mitochondria facilitated intrinsic apoptosis, evidenced by upregulated cytochrome C, caspase 3, and caspase 9. Collectively, our data suggest that the aberrant expression of PI3K/AKT signaling contributes to apoptosis resistance in HCC.
format	article
author	Wang Zhuangqiang Cui Xiaopeng Hao Gaopeng He Jiefeng
author_facet	Wang Zhuangqiang Cui Xiaopeng Hao Gaopeng He Jiefeng
author_sort	Wang Zhuangqiang
title	Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
title_short	Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
title_full	Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
title_fullStr	Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
title_full_unstemmed	Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma
title_sort	aberrant expression of pi3k/akt signaling is involved in apoptosis resistance of hepatocellular carcinoma
publisher	De Gruyter
publishDate	2021
url	https://doaj.org/article/fa72f5e1f7ad49be96fc44c925352846
work_keys_str_mv	AT wangzhuangqiang aberrantexpressionofpi3kaktsignalingisinvolvedinapoptosisresistanceofhepatocellularcarcinoma AT cuixiaopeng aberrantexpressionofpi3kaktsignalingisinvolvedinapoptosisresistanceofhepatocellularcarcinoma AT haogaopeng aberrantexpressionofpi3kaktsignalingisinvolvedinapoptosisresistanceofhepatocellularcarcinoma AT hejiefeng aberrantexpressionofpi3kaktsignalingisinvolvedinapoptosisresistanceofhepatocellularcarcinoma
_version_	1718371876484415488

Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma

Ejemplares similares