LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway

Xu, Rui; Zhang, Yinci; Li, Amin; Ma, Yongfang; Cai, Wenpeng; Wang, Jintao; Xie, Yan; Zhou, Shuping; Cao, Weiya; Tang, Xiaolong

doi:10.3892/mmr.2021.12147

Cited by 20 publications

(12 citation statements)

References 54 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Liver cancers are characterized by severe intratumoral hypoxia with a median pO 2 of 6 mmHg (0.9% O 2 ) compared with 30 mmHg in normal liver tissue ( 174 ). Phosphatidylinositol-3-kinase and AKT signaling also contribute to increased HIF activity in HCC ( 175 ). Increased HIF-1α expression in the HCC diagnostic biopsy is associated with decreased disease-free and overall survival ( 176 ).…”

Section: Targeting Hifs For Cancer Therapymentioning

confidence: 99%

Hypoxia-inducible factors: cancer progression and clinical translation

Wicks¹,

Semenza²

2022

Journal of Clinical Investigation

214

129

View full text Add to dashboard Cite

Hypoxia-inducible factors (HIFs) are master regulators of oxygen homeostasis that match O 2 supply and demand for each of the 50 trillion cells in the adult human body. Cancer cells co-opt this homeostatic system to drive cancer progression. HIFs activate the transcription of thousands of genes that mediate angiogenesis, cancer stem cell specification, cell motility, epithelial-mesenchymal transition, extracellular matrix remodeling, glucose and lipid metabolism, immune evasion, invasion, and metastasis. In this Review, the mechanisms and consequences of HIF activation in cancer cells are presented. The current status and future prospects of small-molecule HIF inhibitors for use as cancer therapeutics are discussed.

show abstract

Section: Targeting Hifs For Cancer Therapymentioning

confidence: 99%

Hypoxia-inducible factors: cancer progression and clinical translation

Wicks¹,

Semenza²

2022

Journal of Clinical Investigation

214

129

View full text Add to dashboard Cite

show abstract

“…Indirubin has also been reported to exert anticancer effects in human cancers (Li Z. et al, 2020). LY-294002 enhances the chemosensitivity of liver cancer to oxaliplatin (Xu et al, 2021). We found here these small-molecule perturbagens might have favorable therapeutic effects for patients in cluster 1, who had the high expression of their target genes.…”

Section: Discussionmentioning

confidence: 53%

Chromatin Separation Regulators Predict the Prognosis and Immune Microenvironment Estimation in Lung Adenocarcinoma

Han

et al. 2022

Front. Genet.

View full text Add to dashboard Cite

Background: Abnormal chromosome segregation is identified to be a common hallmark of cancer. However, the specific predictive value of it in lung adenocarcinoma (LUAD) is unclear.Method: The RNA sequencing and the clinical data of LUAD were acquired from The Cancer Genome Atlas (TACG) database, and the prognosis-related genes were identified. The Kyoto Encyclopedia of Genes and Genomes (KEGG) and Gene Ontology (GO) were carried out for functional enrichment analysis of the prognosis genes. The independent prognosis signature was determined to construct the nomogram Cox model. Unsupervised clustering analysis was performed to identify the distinguishing clusters in LUAD-samples based on the expression of chromosome segregation regulators (CSRs). The differentially expressed genes (DEGs) and the enriched biological processes and pathways between different clusters were identified. The immune environment estimation, including immune cell infiltration, HLA family genes, immune checkpoint genes, and tumor immune dysfunction and exclusion (TIDE), was assessed between the clusters. The potential small-molecular chemotherapeutics for the individual treatments were predicted via the connectivity map (CMap) database.Results: A total of 2,416 genes were determined as the prognosis-related genes in LUAD. Chromosome segregation is found to be the main bioprocess enriched by the prognostic genes. A total of 48 CSRs were found to be differentially expressed in LUAD samples and were correlated with the poor outcome in LUAD. Nine CSRs were identified as the independent prognostic signatures to construct the nomogram Cox model. The LUAD-samples were divided into two distinct clusters according to the expression of the 48 CSRs. Cell cycle and chromosome segregation regulated genes were enriched in cluster 1, while metabolism regulated genes were enriched in cluster 2. Patients in cluster 2 had a higher score of immune, stroma, and HLA family components, while those in cluster 1 had higher scores of TIDES and immune checkpoint genes. According to the hub genes highly expressed in cluster 1, 74 small-molecular chemotherapeutics were predicted to be effective for the patients at high risk.Conclusion: Our results indicate that the CSRs were correlated with the poor prognosis and the possible immunotherapy resistance in LUAD.

show abstract

“…IGF-1R is a transmembrane tyrosine protein kinase receptor [ 18 , 19 ]. When IGF-1R binds to the corresponding ligand, IGF-1, it catalyzes the phosphorylation of autophosphorylation sites and causes intracellular signal transduction [ 19 , 20 ].…”

Section: Discussionmentioning

confidence: 99%

“…The tumors in most patients with advanced HCC that are treated with the first-line drug, sorafenib, develop drug resistance [14,15]. Sorafenib-acquired resistance reportedly involves a variety of mechanisms, including multiple-signal pathway crosstalk; abnormal expression of tyrosine kinase receptors, such as PDGFR-β, c-kit, Flt-3, VEGFR and EGFR; epithelial-mesenchymal transition (EMT); and cancer stem-cell differentiation [16][17][18]. In this work, we demonstrated that IGF-1R decreased the sensitivity of HCC to sorafenib treatment; down-regulation of IGF-1R increased the inhibition of sorafenib on the migration of HCC cells mainly through PI3K/Akt and Ras/Raf/ERK pathways.…”

Section: Discussionmentioning

confidence: 99%

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Cai

Wang

et al. 2023

BMC Cancer

Self Cite

View full text Add to dashboard Cite

Background Insulin-like growth factor-1 receptor (IGF-1R) promotes cell proliferation and migration and inhibitsapoptosis, all of which can contribute to the development of cancers. Method This study investigated the effect and mechanism of IGF-1R in mediating the desensitization of hepatocellular carcinoma (HCC) to sorafenib. Results IGF-1R, highly expressed in the HCC cell lines SK-Hep1 and HepG2, promotes cell proliferation, migration, and anti-apoptosis through PI3K / Akt and RAS / Raf / ERK signaling pathways, resulting in HCC resistance to sorafenib. Knockdown of IGF-1R by RNA interference decreased proliferation and cell migration and upregulation of sorafenib-induced apoptosis of HCC cells. In vivo studies demonstrated that IGF-1R knockdown inhibited the growth of SK-Hep1 xenografts. Conclusion These data are evidence that IGF-1R participates in regulating the survival and cell growth of HCC through the PI3K / Akt and RAS / Raf / ERK signaling pathways. Intervention in the expression of IGF-1R may increase the inhibitory effect of sorafenib on HCC.

show abstract

LY‑294002 enhances the chemosensitivity of liver cancer to oxaliplatin by blocking the PI3K/AKT/HIF‑1α pathway

Cited by 20 publications

References 54 publications

Hypoxia-inducible factors: cancer progression and clinical translation

Hypoxia-inducible factors: cancer progression and clinical translation

Chromatin Separation Regulators Predict the Prognosis and Immune Microenvironment Estimation in Lung Adenocarcinoma

IGF-1R down regulates the sensitivity of hepatocellular carcinoma to sorafenib through the PI3K / akt and RAS / raf / ERK signaling pathways

Contact Info

Product

Resources

About