Activation of PI3 kinase/Akt/HIF-1α pathway contributes to hypoxia-induced epithelial-mesenchymal transition and chemoresistance in hepatocellular carcinoma.

Content Provider	Semantic Scholar
Author	Jiao, Min Nan, Kejun
Copyright Year	2011
Abstract	Hypoxia is known to promote malignant progression and to induce chemoresistance in cancer. However, the exact mechanisms driving hypoxia induced malignance remain elusive. We found that with exposure to hypoxic condition, hepatocellular carcinoma (HCC) cells experienced epithelial-mesenchymal transition (EMT), with increased cell migration and invasion, and exhibited high resistance to chemotherapy. We demonstrated that hypoxia-induced EMT and chemoresistance were accompanied by increased HIF-1α expression and activation of Akt. HIF-1α could be blocked by PI3K inhibitor LY294002, indicating HIF-1α activation was regulated by PI3K/Akt pathway. Furthermore, we showed that inhibition of PI3K/Akt and HIF-1α enhanced the therapeutic efficacy of hypoxic chemotherapy in the HCC xenograft model. Our findings indicate that the activation of PI3K/Akt/HIF-1α pathway plays a critical role in mediating hypoxia-induced EMT and drug resistance leading to unfavorable treatment outcome. Our study provides novel insights into the malignant progression triggered by hypoxic microenvironment in HCC cells.
Starting Page	58
Ending Page	66
Page Count	9
File Format	PDF HTM / HTML
Alternate Webpage(s)	https://www.spandidos-publications.com/ijo/40/2/461/download
PubMed reference number	21922131v1
Alternate Webpage(s)	https://doi.org/10.3892/ijo.2011.1197
DOI	10.3892/ijo.2011.1197
Journal	International journal of oncology
Volume Number	40
Issue Number	2
Language	English
Access Restriction	Open
Subject Keyword	1-Phosphatidylinositol 3-Kinase Hypoxia LY 294002 Liver carcinoma Neoplasms Proto-Oncogene Proteins c-akt Xenograft type of graft
Content Type	Text
Resource Type	Article