La voie de signalisation PI3K-AKT-mTOR : description, développement thérapeutique, résistances, marqueurs prédictifs/pronostiques et applications thérapeutiques en cancérologie

Brotelle, Thibault; Bay, Jacques‐Olivier

doi:10.1016/j.bulcan.2015.09.011

Cited by 26 publications

(12 citation statements)

References 43 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Notably, sorafenib can activate the PI3K/AKT signaling pathway in hepatoma cells while achieving certain therapeutic effects. As a classic signal transduction pathway against apoptosis and promoting survival, the PI3K/AKT pathway participates in the regulation of multiple cell activities and plays an unusual role in tumor-targeted drug resistance [27]. Other studies have also confirmed that AKT is involved in the drug resistance of hepatocellular carcinoma cells to sorafenib.…”

Section: Discussionmentioning

confidence: 99%

Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

Zhang

Zhi

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

Background Sorafenib, a multiple-target-point kinase inhibitor, has been used as a standard treatment for advanced liver cancer and has shown therapeutic benefits. However, resistance often occurs, prompting the need for identification of synergizing agents. Celastrol is a major active ingredient of Tripterygium wilfordii, which can increase the antitumor effect of traditional antitumor drugs. This work focused on the sensitization of liver cancers in use of celastrol combined with sorafenib. Material/Methods The IC50 values of sorafenib and celastrol on cancer cells were determined through MTT assays. The effects of sorafenib on AKT signaling and VEGF levels in sorafenib-treated cancer cells were analyzed by Western blotting and ELISA, respectively. After combined treatment with celastrol and sorafenib, the survival rate of tumor cells was determined by MTT and clonogenic assays, and the apoptosis rate was also determined by flow cytometry. In addition, the in vivo antitumor activity of celastrol combined with sorafenib was evaluated in Hepa1-6 tumor-bearing mice. Results Sorafenib treatment induced the compensatory activation of the AKT pathway and autocrine VEGF in hepatoma cells, which could be reversed by celastrol. Furthermore, celastrol enhanced the growth inhibition and apoptosis induction of cancer cells by sorafenib both in vitro and in vivo and reduced the dosage of sorafenib needed. Conclusions Celastrol enhances the antitumor activity of sorafenib in HCC tumor cells by suppressing the AKT pathway and VEGF autocrine system.

show abstract

Section: Discussionmentioning

confidence: 99%

Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

Zhang

Zhi

et al. 2019

Med Sci Monit

View full text Add to dashboard Cite

show abstract

“…The Akt pathway is a well-known important signaling pathway involved in the regulation of many cellular functions, such as metabolism, survival, apoptosis and chemotherapy resistance. 32 Recent studies show that the Akt pathway is hyperactivated in various human malignancies including AML. 33 Constitutive activation of the Akt pathway may contribute to cancer progression and chemotherapy resistance in AML.…”

Section: Discussionmentioning

confidence: 99%

TUG1 knockdown enhances adriamycin cytotoxicity by inhibiting glycolysis in adriamycin-resistant acute myeloid leukemia HL60/ADR cells

et al. 2019

View full text Add to dashboard Cite

show abstract

“…The PI3K/AKT/mTOR signaling pathway plays a vital role in a variety of biological and physiological processes, and survival, growth transcription, and translation, are mostly related to the occurrence of MDR 71 , 72 . Abnormal activation of the PI3K/AKT/mTOR pathway helps tumors to produce MDR, such as acute myeloid leukemia (AML) and ovarian cancer 73 , 74 .…”

Section: Aberrant Activation Of the Pi3k/akt/nf-κb And Pi3k/akt/mtor mentioning

confidence: 99%

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

et al. 2020

View full text Add to dashboard Cite

Multidrug resistance (MDR) is the dominant challenge in the failure of chemotherapy in cancers. Phosphatidylinositol 3-kinase (PI3K) is a lipid kinase that spreads intracellular signal cascades and regulates a variety of cellular processes. PI3Ks are considered significant causes of chemoresistance in cancer therapy. Protein kinase B (AKT) is also a significant downstream effecter of PI3K signaling, and it modulates several pathways, including inhibition of apoptosis, stimulation of cell growth, and modulation of cellular metabolism. This review highlights the aberrant activation of PI3K/AKT as a key link that modulates MDR. We summarize the regulation of numerous major targets correlated with the PI3K/AKT pathway, which is further related to MDR, including the expression of apoptosis-related protein, ABC transport and glycogen synthase kinase-3 beta (GSK-3β), synergism with nuclear factor kappa beta (NF-κB) and mammalian target of rapamycin (mTOR), and the regulation of glycolysis.

show abstract

La voie de signalisation PI3K-AKT-mTOR : description, développement thérapeutique, résistances, marqueurs prédictifs/pronostiques et applications thérapeutiques en cancérologie

Cited by 26 publications

References 43 publications

Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

Celastrol Enhances the Anti-Liver Cancer Activity of Sorafenib

TUG1 knockdown enhances adriamycin cytotoxicity by inhibiting glycolysis in adriamycin-resistant acute myeloid leukemia HL60/ADR cells

PI3K/AKT pathway as a key link modulates the multidrug resistance of cancers

Contact Info

Product

Resources

About