In conclusion, the data of this study suggested that naringin presented anti-tumor effects in TC cells through inhibiting TC cell proliferation and inducing cell apoptosis via regulating the expression of cell proliferation and apoptosis related genes and PI3K/AKT pathway activation.
<b>Conclusions</b>: Our data demonstrate that vitamin C kills thyroid cancer cells by inhibiting MAPK/ERK and PI3K/AKT pathways via a ROS-dependent mechanism and suggest that pharmaceutical concentration of vitamin C has potential clinical use in thyroid cancer therapy.
Genetic alterations in pathways, including the mitogen‑activated protein kinase (MAPK)/extracellular signal‑regulated kinase (Erk) and phosphatidylinositol‑3‑kinase (PI3K)/protein kinase B (Akt) pathways, are the driving force behind the development of differentiated thyroid cancer cases into aggressive and undifferentiated forms of thyroid cancer.
Long Noncoding RNA LINC003121 Inhibits Proliferation and Invasion of Thyroid Cancer Cells by Suppression of the Phosphatidylinositol-3-Kinase (PI3K)/Akt Signaling Pathway.
In conclusion, our data define a novel mechanism of PI3K/AKT hyperactivation and outline a regulatory role for miR-146b in suppressing PTEN expression, a frequent observation in thyroid cancer.
Mechanically, our data demonstrated that tumor-promoting role of N-cadherin in thyroid cancer was closely related to the activities of the MAPK/Erk, the phosphatidylinositol-3-kinase (PI3K)/Akt and p16/Rb signaling pathways in addition to affecting the EMT process.
Our aim was to determine the therapeutic efficacy of simultaneously targeting these pathways in thyroid cancer with a single agent and to evaluate biomarkers of treatment response.<b>Experimental Design:</b> CUDC-907 is a first-in-class compound, functioning as a dual inhibitor of HDACs and the PI3K/AKT pathway.
The initiation of thyroid cancer is often triggered by a genetic mutation in the phosphortidylinositol-3 kinase (PI3K) or mitogen-activated protein kinase (MAPK) pathway, such as <i>RAS</i> and <i>BRAF</i>, or by the rearrangement of growth factor receptor tyrosine kinase genes such as <i>RET/PTC</i>.
Thyroid cancer (TC) is frequently associated with BRAF or RAS oncogenic mutations and RET/PTC rearrangements, with aberrant RAF-MEK-ERK and/or PI3K pathway activation.
Demethylating the hypermethylated REC8 gene restored its expression in thyroid cancer cells in which the PI3K pathway was genetically over-activated and induced expression of REC8 protein inhibited the proliferation and colony formation of these cells.
Treatment of the most resistant cell line, 8505c, using lexatumumab in combination with the BRAF(V600E) inhibitor, PLX4720, and the PI3K inhibitor, LY294002, (triple-drug combination) sensitizes the cells by triggering both the extrinsic and intrinsic apoptotic pathways in vitro as well as 8505c orthotopic thyroid tumors in vivo.
Our findings suggest that miR-145 is a master regulator of thyroid cancer growth, mediates its effect through the PI3K/Akt pathway, is secreted by the thyroid cancer cells, and may serve as an adjunct biomarker for thyroid cancer diagnosis.
These distinct genetic alterations constitutively activate the MAPK, PI3K and β-catenin signaling pathways, which have been implicated in thyroid cancer development and progression.
Initiation and progression of thyroid cancer involves multiple genetic and epigenetic alterations, of which mutations leading to the activation of the MAPK and PI3K-AKT signaling pathways are crucial.
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.