scholarly journals Apoptosis Activation in Thyroid Cancer Cells by Jatrorrhizine-Platinum(II) Complex via Downregulation of PI3K/AKT/Mammalian Target of Rapamycin (mTOR) Pathway

2020 ◽  
Vol 26 ◽  
Author(s):  
KeBin Lu ◽  
Wenjun Wei ◽  
Jiaqian Hu ◽  
Duo Wen ◽  
Ben Ma ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Mammalian Target Of Rapamycin ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Thyroid Cancer Cells

scholarly journals The Akt-Specific Inhibitor MK2206 Selectively Inhibits Thyroid Cancer Cells Harboring Mutations That Can Activate the PI3K/Akt Pathway

2011 ◽  
Vol 96 (4) ◽  
pp. E577-E585 ◽  
Author(s):  
Ruixin Liu ◽  
Dingxie Liu ◽  
Eliana Trink ◽  
Ermal Bojdani ◽  
Guang Ning ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Therapeutic Potential ◽  
Mammalian Target Of Rapamycin ◽  
Specific Inhibitor ◽  
Akt Pathway ◽  
Akt Inhibitor ◽  
Cancer Cell Growth ◽  
Ic50 Values ◽  
Thyroid Cancer Cells

Abstract Context: The phosphoinositide 3-kinase (PI3K)/Akt pathway is widely postulated to be an effective therapeutic target in thyroid cancer. Objective: The aim of the study was to test the therapeutic potential of the novel Akt inhibitor MK2206 for thyroid cancer. Design: We examined the effects of MK2206 on thyroid cancer cells with respect to the genotypes of the PI3K/Akt pathway. Results: Proliferation of thyroid cancer cells OCUT1, K1, FTC133, C643, Hth7, and TPC1, which harbored PIK3CA, PTEN, Ras, or RET/PTC mutations that could activate the PI3K/Akt pathway, was potently inhibited by MK2206 with IC50 values mostly below or around 0.5 μm. In contrast, no potent inhibition by MK2206 was seen in most of the Hth74, KAT18, SW1736, WRO, and TAD2 cells that did not harbor mutations in the PI3K/Akt pathway. The inhibition efficacy was also genetic-selective. Specifically, the average inhibition efficacies were 59.2 ± 11.3 vs. 36.4 ± 8.8% (P = 0.005) at 1 μm MK2206 and 64.4 ± 11.5 vs. 38.5 ± 18.9% (P = 0.02) at 3 μm MK2206 for cells with mutations vs. cells without. The SW1736 cell, lacking mutations in the PI3K/Akt pathway, had minimal response to MK2206, but transfection with exogenous PIK3CA mutants, PIK3CA H1047R and E545K, significantly increased its sensitivity to MK2206. MK2206 also completely overcame the feedback activation of Akt from temsirolimus-induced mammalian target of rapamycin suppression, and the two inhibitors synergistically inhibited thyroid cancer cell growth. Conclusions: Our study demonstrates a genetic selectivity of MK2206 in inhibiting thyroid cancer cells by targeting the PI3K/Akt pathway, supporting a clinical trial in thyroid cancer.

scholarly journals Adenosine 5'‐monophosphate‐activated protein kinase‐dependent mTOR pathway is involved in flavokawain B‐induced autophagy in thyroid cancer cells

2018 ◽  
Vol 109 (8) ◽  
pp. 2576-2589 ◽  
Author(s):  
Qin He ◽  
Wenping Liu ◽  
Sha Sha ◽  
Shanshan Fan ◽  
Yajing Yu ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Protein Kinase ◽  
Cancer Cells ◽  
Mtor Pathway ◽  
Thyroid Cancer Cells

scholarly journals Dual Inhibition of Mitogen-Activated Protein Kinase Kinase and Mammalian Target of Rapamycin in Differentiated and Anaplastic Thyroid Cancer

2009 ◽  
Vol 23 (11) ◽  
pp. 1937-1937
Author(s):  
Ning Jin ◽  
Tianyun Jiang ◽  
D. Marc Rosen ◽  
Barry D. Nelkin ◽  
Douglas W. Ball
Keyword(s):  
Thyroid Cancer ◽  
Growth Inhibition ◽  
Differentiated Thyroid Cancer ◽  
Mammalian Target Of Rapamycin ◽  
Xenograft Model ◽  
Anaplastic Thyroid Cancer ◽  
Mtor Pathway ◽  
Target Of Rapamycin ◽  
Mtor Inhibition ◽  
Pathway Inhibition

ABSTRACT Context Differentiated thyroid cancer and anaplastic thyroid cancer tumors frequently have activation of the ras/raf /MAPK kinase (MEK)/ERK and phosphatidylinositol 3-kinase (PI-3K)/AKT/mammalian target of rapamycin (mTOR) signaling pathways. Objective The objective of the study was to investigate the efficacy of MEK and mTOR inhibitors in preclinical thyroid cancer treatment models with defined mutation status. Experimental Design The MEK inhibitor AZD6244 (ARRY-142886) and mTOR inhibitor rapamycin were tested separately and in combination in 10 differentiated thyroid cancer and anaplastic thyroid cancer cell lines and in a xenograft model for evidence of pathway inhibition, growth inhibition, apoptosis, and long-range adaptation and resistance. Results Seven of 10 tested lines had evidence of significant basal activity of the PI-3K/AKT/mTOR pathway, with elevated phosphorylated AKT and phosphorylated p70 S6 kinase. Activation of ras/RAF/MEK/ERK was equally common in this panel. All 10 lines exhibited better than 60% growth inhibition with combined MEK and mTOR inhibition, including lines with BRAF, Ret-PTC, ras, and PTEN mutations. Rapamycin or AZD6244 alone achieved this threshold in six and two lines, respectively. Dual-pathway inhibition in the Ret-PTC mutant cell line TPC1 caused an intense G1 arrest in cell culture and reversible cytostatic inhibition in a xenograft model. We did not observe significant feedback up-regulation of AKT activation in either acute or prolonged exposures. Conclusion These preclinical results support the inclusion of thyroid cancer patients in early-phase clinical trials combining ras/RAF/MEK/ERK and PI-3K/AKT/mTOR pathway inhibition.

Mitochondrial mass and function is regulated by PI3K signaling in thyroid cancer cells

2013 ◽  
Author(s):  
K Alexander Iwen ◽  
Erich Schroder ◽  
Julia Resch ◽  
Ulrich Lindner ◽  
Peter Konig ◽  
...  
Keyword(s):  
Thyroid Cancer ◽  
Cancer Cells ◽  
Pi3k Signaling ◽  
Mitochondrial Mass ◽  
And Function ◽  
Thyroid Cancer Cells
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