ArticleOpen life sciences2021
Aberrant expression of PI3K/AKT signaling is involved in apoptosis resistance of hepatocellular carcinoma.
Article in Open life sciences, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed, 18 citations in OpenAlex.
- Upregulation of LTF promotes left-sided colorectal cancer development via activating PI3K/AKT pathway.Cell adhesion & migration · 2026Article
- Molecular Signaling Pathways, Regulatory and Coactivator Networks, and Emerging Mechanisms in Hepatocellular Carcinoma.Biomedicines · 2026Review
- Deciphering the Medicinal Chemistry Aspects of Akt Inhibitors for the Management of Cancer: Structure-Activity Relationship Frameworks, Landscapes, and Optimization Approaches.Chemistry & biodiversity · 2026Review
- The Role of miRNA-21 in the Metastasis of Hepatocellular Carcinoma as a Therapeutic Target.International journal of hematology-oncology and stem cell research · 2026Review
- [HDAC2-mediated H3K27 acetylation promotes the proliferation and migration of hepatocellular carcinoma cells].Beijing da xue xue bao. Yi xue ban = Journal of Peking University. Health sciences · 2025Article
- Review
- Deciphering STAT3 signaling potential in hepatocellular carcinoma: tumorigenesis, treatment resistance, and pharmacological significance.Cellular & molecular biology letters · 2023Review
- New insights into fibrotic signaling in hepatocellular carcinoma.Frontiers in oncology · 2023Review
- Overexpression ofMolecules and cells · 2022Article
- Protein phosphatases regulate the liver microenvironment in the development of hepatocellular carcinoma.Experimental & molecular medicine · 2022Review
- Article
- A cellular senescence-related genes model allows for prognosis and treatment stratification of hepatocellular carcinoma: A bioinformatics analysis and experimental verification.Frontiers in genetics · 2022Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
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.
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