New liver cancer biomarkers: PI3K/AKT/mTOR pathway members and eukaryotic translation initiation factors

Golob-Schwarzl, Nicole; Krassnig, Stefanie; Toeglhofer, Anna M.; Park, Young Nyun; Gogg-Kamerer, Margit; Vierlinger, Klemens; Schröder, Fabian; Rhee, Hyungjn; Schicho, Rudolf; Fickert, Peter; Haybaeck, Johannes

doi:10.1016/j.ejca.2017.06.003

Cited by 85 publications

(66 citation statements)

References 42 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PI3K/AKT/mTOR pathway, playing an important role in the survival and proliferation of tumor cells and having carcinogenic potential, is one of the most common activation signal cascades in HCC [6,7]. Moreover, this pathway also regulates the expression of hypoxia-inducible factor (HIF)-1α [8,9].…”

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

Tang

Xie

et al. 2020

Nanoscale Res Lett

View full text Add to dashboard Cite

Polymer materials encapsulating drugs have broad prospects for drug delivery. We evaluated the effectiveness of polyethylene glycol-poly (lactic-co-glycolic acid) (PLGA-PEG) encapsulation and release characteristics of PI3K/mTOR inhibitor NVP-BEZ235 (BEZ235). We proposed a strategy for targeting radiosensitization of liver cancer cells. The biocompatibility, cell interaction, and internalization of Glypican-3 (GPC3) antibody-modified, BEZ235-loaded PLGA-PEG nanoparticles (NP-BEZ235-Ab) in hepatoma cells in vitro were studied. Also, the cell killing effect of NP-BEZ235-Ab combined with γ-ray cell was evaluated. We used confocal microscopy to monitor nanoparticle-cell interactions and cellular uptake, conducted focus-formation experiments to analyze the synergistic biological effects of NP-BEZ235-Ab and priming, and studied synergy in liver cancer cells using molecular biological methods such as western blotting. We found that PLGA-PEG has good loading efficiency for BEZ235 and high selectivity to GPC3-positive HepG2 liver cancer cells, thus documenting that NP-BEZ235-Ab acts as a small-molecule drug delivery nanocarrier. At the nominal concentration, the NP-BEZ235-Ab nanoformulation synergistically kills liver cancer cells with significantly higher efficiency than does the free drug. Thus, NP-BEZ235-Ab is a potential radiosensitizer.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

Tang

Xie

et al. 2020

Nanoscale Res Lett

View full text Add to dashboard Cite

show abstract

“…PI3K/AKT signaling pathway is an important signaling pathway responsible for malignant cancer cells proliferation, apoptosis, invasion, metastasis, and angiogenesis. Previous studies have shown the PI3K/AKT path way is overactivated in some HCC cases and PI3K/AKT over-activation is associated with poor prognosis in HCC patients (Minguez et al, 2009;Golob-Schwarzl et al, 2017). It has been revealed that PI3K/AKT activation enhances the transcriptional activity of HIF-1a, further inducing VEGF expression (Zhang et al, 2015).…”

Section: Discussionmentioning

confidence: 99%

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

Ren

Yang

et al. 2020

Front. Pharmacol.

View full text Add to dashboard Cite

Recent studies have revealed that natural plants-derived polysaccharides exhibit potent anti-tumor activity. Our earlier studies suggest that dandelion polysaccharide (DP) inhibits hepatocellular carcinoma (HCC) cell proliferation in vitro and in vivo. Here, we investigated the effects of DP on the angiogenesis of HCC and the potential molecular mechanisms by which DP regulates angiogenesis. Wound-healing and transwell invasion assays revealed that DP inhibited HUVECs migration and invasion in vitro, respectively. Tube formation assay, chick chorioallantoic membrane (CAM) assay, and immunohistochemistry (IHC) demonstrated that DP suppressed vasculogenesis in vitro and in vivo. Moreover, Western blot and immunofluorescence staining verified that DP treatment decreased the protein levels of some key factors involved in angiogenesis of HCC, such as hypoxia-inducible factor 1a (HIF-1a), vascular endothelial growth factor (VEGF), p-PI3K, and p-AKT. However, activation of PI3K/AKT pathway with insulin-like growth factor 1 (IGF-1) treatment attenuated the effect of DP on angiogenesis via lowering the expression of HIF-1a and VEGF. In summary, we found that DP treatment inhibited angiogenesis in vivo and in vitro through suppressing expression of VEGF and HIF-1a. Furthermore, we showed that the expression of VEGF and HIF1-a was modulated by PI3K/AKT signaling. Collectively, our study suggests that DP is a promising anti-cancer drug candidate for treating HCC.

show abstract

“…This pathway is involved in many types of cellular processes including survival, proliferation, metastasis, metabolism and angiogenesis [13][14][15]. Given the frequent hyperactivation or deregulation of Akt/mTOR pathway in HCC [15][16][17], several small molecule inhibitors targeting this pathway have been developed and are currently undergoing preclinical or clinical trials [8,18].…”

Section: Introductionmentioning

confidence: 99%

Haprolid Inhibits Tumor Growth of Hepatocellular Carcinoma through Rb/E2F and Akt/mTOR Inhibition

Xing

Bhuria

Bui

et al. 2020

Cancers

View full text Add to dashboard Cite

Background: Hepatocellular carcinoma (HCC) represents a major health burden with limited curative treatment options. There is a substantial unmet need to develop innovative approaches to impact the progression of advanced HCC. Haprolid is a novel natural component isolated from myxobacteria. Haprolid has been reported as a potent selective cytotoxin against a panel of tumor cells in recent studies including HCC cells. The aims of this study are to evaluate the antitumor effect of haprolid in HCC and to understand its underlying molecular mechanisms. Methods: The efficacy of haprolid was evaluated in human HCC cell lines (Huh-7, Hep3B and HepG2) and xenograft tumors (NMRI-Foxn1 nu mice with injection of Hep3B cells). Cytotoxic activity of haprolid was determined by the WST-1 and crystal violet assay. Wound healing, transwell and tumorsphere assays were performed to investigate migration and invasion of HCC cells. Apoptosis and cell-cycle distribution were measured by flow cytometry. The effects of haprolid on the Rb/E2F and Akt/mTOR pathway were examined by immunoblotting and immunohistochemistry. Results: haprolid treatment significantly inhibited cell proliferation, migration and invasion in vitro. The epithelial-mesenchymal transition (EMT) was impaired by haprolid treatment and the expression level of N-cadherin, vimentin and Snail was downregulated. Moreover, growth of HCC cells in vitro was suppressed by inhibition of G1/S transition, and partially by induction of apoptosis. The drug induced downregulation of cell cycle regulatory proteins cyclin A, cyclin B and CDK2 and induced upregulation of p21 and p27. Further evidence showed that these effects of haprolid were associated with Rb/E2F downregulation and Akt/mTOR inhibition. Finally, in vivo nude mice experiments demonstrated significant inhibition of tumor growth upon haprolid treatment. Conclusion: Our results show that haprolid inhibits the growth of HCC through dual inhibition of Rb/E2F and Akt/mTOR pathways. Therefore, haprolid might be considered as a new and promising candidate for the palliative therapy of HCC.

show abstract

New liver cancer biomarkers: PI3K/AKT/mTOR pathway members and eukaryotic translation initiation factors

Cited by 85 publications

References 42 publications

RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

RETRACTED ARTICLE: The PI3K/mTOR dual inhibitor BEZ235 nanoparticles improve radiosensitization of hepatoma cells through apoptosis and regulation DNA repair pathway

Dandelion Polysaccharide Exerts Anti-Angiogenesis Effect on Hepatocellular Carcinoma by Regulating VEGF/HIF-1α Expression

Haprolid Inhibits Tumor Growth of Hepatocellular Carcinoma through Rb/E2F and Akt/mTOR Inhibition

Contact Info

Product

Resources

About