ArticlePloS one2012
Activation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop is involved in rapamycin resistance in hepatocellular carcinoma.
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed, 60 citations in OpenAlex.
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- In Silico Analysis of MicroRNA Expression Data in Liver Cancer.Cancer informatics · 2023Article
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- Genomic clustering analysis identifies molecular subtypes of thymic epithelial tumors independent of World Health Organization histologic type.Oncotarget · 2021Article
- Article
- Novel molecular targets in hepatocellular carcinoma.World journal of clinical oncology · 2020Review
- Human amniotic membrane conditioned medium inhibits proliferation and modulates related microRNAs expression in hepatocarcinoma cells.Scientific reports · 2019Article
- Mechanisms of skeletal muscle wasting in a mouse model for myotonic dystrophy type 1.Human molecular genetics · 2018Article
- Inhibition of the PI3K/Akt signaling pathway reverses sorafenib-derived chemo-resistance in hepatocellular carcinoma.Oncology letters · 2018Article
- OIP5, a target of miR-15b-5p, regulates hepatocellular carcinoma growth and metastasis through the AKT/mTORC1 and β-catenin signaling pathways.Oncotarget · 2017Article
- Metformin potentiates the effect of arsenic trioxide suppressing intrahepatic cholangiocarcinoma: roles of p38 MAPK, ERK3, and mTORC1.Journal of hematology & oncology · 2017Article
- IRE1α-XBP1 pathway promotes melanoma progression by regulating IL-6/STAT3 signaling.Journal of translational medicine · 2017Article
- The synergistic inhibition of breast cancer proliferation by combined treatment with 4EGI-1 and MK2206.Cell cycle (Georgetown, Tex.) · 2015Article
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRapamycin is an attractive approach for the treatment and prevention of HCC recurrence after liver transplantation. However, the objective response rates of rapamycin achieved with single-agent therapy were modest, supporting that rapamycin resistance is a frequently observed characteristic of many cancers. Some studies have been devoted to understanding the mechanisms of rapamycin resistance, however, the mechanisms are cell-type-dependent and studies on rapamycin resistance in HCC are extremely limited. METHODOLOGY/PRINCIPAL
findingsThe anti-tumor sensitivity of rapamycin was modest in vitro and in vivo. In both human and rat HCC cells, rapamycin up-regulated the expression and phosphorylation of PDGFRβ in a time and dose-dependent manner as assessed by RT-PCR and western blot analysis. Using siRNA mediated knockdown of PDGFRβ, we confirmed that subsequent activation of AKT and ERK was PDGFRβ-dependent and compromised the anti-tumor activity of rapamycin. Then, blockade of this PDGFRβ-dependent feedback loop by sorafenib enhanced the anti-tumor sensitivity of rapamycin in vitro and in an immunocompetent orthotopic rat model of HCC.
conclusionsActivation of PI3K/AKT and MAPK pathway through a PDGFRβ-dependent feedback loop compromises the anti-tumor activity of rapamycin in HCC, and blockade of this feedback loop by sorafenib is an attractive approach to improve the anti-tumor effect of rapamycin, particularly in preventing or treating HCC recurrence after liver transplantation.
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