Targeting the Akt/PI3K Signaling Pathway as a Potential Therapeutic Strategy for the Treatment of Pancreatic Cancer

AbstractThis study is to investigate the effect of the PI3K/Akt signaling pathway on the regulation of BRCA1 subcellular localization in triple-negative breast cancer (TNBC) MDA-MB-231 cells and hormone-sensitive T47D cells. We found that heregulin-activated T47D cells showed more nuclear localization of BRCA1, but BRCA1 nuclear localization decreased after the inhibition of the PI3K signaling pathway. In MDA-MB-231 cells, activation or inhibition of the PI3K signaling pathway did not significantly affect cell apoptosis and BRCA1 nuclear translocation (P > 0.05). However, in T47D cells, the activation of the PI3K pathway significantly increased cell apoptosis (P < 0.05). In the heregulin-activated MDA-MB-231 and T47D cells, the phosphorylation of Akt and BRCA1 was significantly increased (P < 0.05), while that was significantly reduced after PI3K pathway inhibition (P < 0.05). The changing trends of the mRNA levels of Akt and BRCA1 in MDA-MB-231 and T47D cells after PI3K pathway activation or inhibition were consistent with the trends of their proteins. In both MDA-MB-231 and T47D cells, BRCA1 phosphorylation is regulated by the PI3K signaling pathway, but the nuclear localization of BRCA1 is different in these two cell lines. Moreover, the apoptosis rates of these two cell lines are different.

Download Full-text

Design, synthesis and biological evaluation of novel 2,4-disubstituted quinazoline derivatives targeting H1975 cells via EGFR-PI3K signaling pathway

Bioorganic & Medicinal Chemistry ◽

10.1016/j.bmc.2021.116265 ◽

2021 ◽

Vol 43 ◽

pp. 116265

Author(s):

Zhengjie Wang ◽

Limin Liu ◽

Honglin Dai ◽

Xiaojie Si ◽

Luye Zhang ◽

...

Keyword(s):

Signaling Pathway ◽

Biological Evaluation ◽

Pi3k Signaling ◽

Design Synthesis ◽

Pi3k Signaling Pathway ◽

Quinazoline Derivatives ◽

Synthesis And Biological Evaluation

Download Full-text

Short-term effects of triiodothyronine on thyroid hormone receptor alpha by PI3K pathway in adipocytes, 3T3-L1

Arquivos Brasileiros de Endocrinologia & Metabologia ◽

10.1590/0004-2730000003295 ◽

2014 ◽

Vol 58 (8) ◽

pp. 833-837 ◽

Cited By ~ 2

Author(s):

Miriane de Oliveira ◽

Regiane Marques Castro Olimpio ◽

Maria Teresa De Sibio ◽

Fernanda Cristina Fontes Moretto ◽

Renata de Azevedo Mello Luvizotto ◽

...

Keyword(s):

Thyroid Hormone ◽

Mrna Expression ◽

Signaling Pathway ◽

Thyroid Hormone Receptor ◽

Pi3k Pathway ◽

Control Group ◽

Pi3k Signaling ◽

Pi3k Inhibitor Ly294002 ◽

Receptor Alpha ◽

Pi3k Signaling Pathway

Objective The present study aimed to examine the effects of thyroid hormone (TH), more precisely triiodothyronine (T3), on the modulation of TH receptor alpha (TRα) mRNA expression and the involvement of the phosphatidyl inositol 3 kinase (PI3K) signaling pathway in adipocytes, 3T3-L1, cell culture. Materials and methods: It was examined the involvement of PI3K pathway in mediating T3 effects by treating 3T3-L1 adipocytes with physiological (P=10nM) or supraphysiological (SI =100 nM) T3 doses during one hour (short time), in the absence or the presence of PI3K inhibitor (LY294002). The absence of any treatment was considered the control group (C). RT-qPCR was used for mRNA expression analyzes. For data analyzes ANOVA complemented with Tukey’s test was used at 5% significance level. Results T3 increased TRα mRNA expression in P (1.91±0.13, p<0.001), SI (2.14±0.44, p<0.001) compared to C group (1±0.08). This increase was completely abrogated by LY294002 in P (0.53±0.03, p<0.001) and SI (0.31±0.03, p<0.001). To examine whether TRα is directly induced by T3, we used the translation inhibitor cycloheximide (CHX). The presence of CHX completely abrogated levels TRα mRNA in P (1.15±0.05, p>0.001) and SI (0.99±0.15, p>0.001), induced by T3. Conclusion These results demonstrate that the activation of the PI3K signaling pathway has a role in T3-mediated indirect TRα gene expression in 3T3-L1 adipocytes.

Download Full-text