Inspecting the Role of PI3K/AKT Signaling Pathway in Cancer Development Using an In Silico Modeling and Simulation Approach

Background: AKT/PKB is an important enzyme with numerous biological functions, and its overexpression is related to the carcinogenesis. AKT stimulates different signaling pathways that are downstream of activated tyrosine kinases and phosphatidylinositol 3-kinase, hence functions as an important target for anti-cancer drugs. Objective: In this review article, we have interpreted the role of AKT signaling pathways in cancer and natural inhibitory effect of Thymoquinone (TQ) in AKT and its possible mechanism. Method: We have collected the updated information and data on AKT, their role in cancer and inhibitory effect of TQ in AKT signaling pathway from google scholar, PubMed, Web of Science, Elsevier, Scopus and many more. Results: There are many drugs already developed, which can target AKT, but very few among them have passed clinical trials. TQ is a natural compound, mainly found in black cumin, which has been found to have potential anti-cancer activities. TQ targets numerous signaling pathways, including AKT, in different cancers. In fact, many studies revealed that AKT is one of the major targets of TQ. The preclinical success of TQ suggests its clinical studies on cancer. Conclusion: This review article summarizes the role of AKT in carcinogenesis, its potent inhibitors in clinical trials, and how TQ acts as an inhibitor of AKT and TQ’s future as a cancer therapeutic drug.

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Exploring clinically relevant dissolution specifications for oral solid dosage forms of weak acid drugs using an in silico modeling and simulation approach

European Journal of Pharmaceutical Sciences ◽

10.1016/j.ejps.2021.105728 ◽

2021 ◽

Vol 159 ◽

pp. 105728

Author(s):

Atsushi Kambayashi ◽

Chikako Yomota

Keyword(s):

Modeling And Simulation ◽

In Silico ◽

Weak Acid ◽

Dosage Forms ◽

Simulation Approach ◽

Solid Dosage Forms ◽

Solid Dosage ◽

In Silico Modeling

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Role of Akt signaling pathway regulation in the speckled mousebird (Colius striatus) during torpor displays tissue specific responses

Cellular Signalling ◽

10.1016/j.cellsig.2020.109763 ◽

2020 ◽

Vol 75 ◽

pp. 109763

Author(s):

Stuart R. Green ◽

Rasha Al-Attar ◽

Andrew E. McKechnie ◽

Samantha Naidoo ◽

Kenneth B. Storey

Keyword(s):

Signaling Pathway ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Tissue Specific ◽

Pathway Regulation

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CEMIP promotes ovarian cancer development and progression via the PI3K/AKT signaling pathway

Biomedicine & Pharmacotherapy ◽

10.1016/j.biopha.2019.108787 ◽

2019 ◽

Vol 114 ◽

pp. 108787 ◽

Cited By ~ 8

Author(s):

Fan Shen ◽

Zhi-hong Zong ◽

Yao Liu ◽

Shuo Chen ◽

Xiu-jie Sheng ◽

...

Keyword(s):

Ovarian Cancer ◽

Signaling Pathway ◽

Akt Signaling ◽

Cancer Development ◽

Akt Signaling Pathway

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The tRNA-derived fragment 5026a inhibits the proliferation of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway

Stem Cell Research & Therapy ◽

10.1186/s13287-021-02497-1 ◽

2021 ◽

Vol 12 (1) ◽

Author(s):

Linwen Zhu ◽

Zhe Li ◽

Xiuchong Yu ◽

Yao Ruan ◽

Yijing Shen ◽

...

Keyword(s):

Gastric Cancer ◽

Cell Cycle ◽

Cancer Cells ◽

Signaling Pathway ◽

Cell Lines ◽

Akt Signaling ◽

Akt Signaling Pathway ◽

Gastric Cancer Cells ◽

Qrt Pcr

Abstract Background Recently, tRNA-derived fragments (tRFs) have been shown to serve important biological functions. However, the role of tRFs in gastric cancer has not been fully elucidated. This study aimed to identify the tumor suppressor role of tRF-5026a (tRF-18-79MP9P04) in gastric cancer. Methods Quantitative reverse transcription-polymerase chain reaction (qRT-PCR) was first used to detect tRF-5026a expression levels in gastric cancer tissues and patient plasma. Next, the relationship between tRF-5026a levels and clinicopathological features in gastric cancer patients was assessed. Cell lines with varying tRF-5026a levels were assessed by measuring tRF-5026a using qRT-PCR. After transfecting cell lines with a tRF-5026a mimic or inhibitor, cell proliferation, colony formation, migration, apoptosis, and cell cycle were evaluated. The expression levels of related proteins in the PTEN/PI3K/AKT pathway were also analyzed by Western blotting. Finally, the effect of tRF-5026a on tumor growth was tested using subcutaneous tumor models in nude mice. Results tRF-5026a was downregulated in gastric cancer patient tissues and plasma samples. tRF-5026a levels were closely related to tumor size, had a certain diagnostic value, and could be used to predict overall survival. tRF-5026a was also downregulated in gastric cancer cell lines. tRF-5026a inhibited the proliferation, migration, and cell cycle progression of gastric cancer cells by regulating the PTEN/PI3K/AKT signaling pathway. Animal experiments showed that upregulation of tRF-5026a effectively inhibited tumor growth. Conclusions tRF-5026a (tRF-18-79MP9P04) is a promising biomarker for gastric cancer diagnostics and has tumor suppressor effects mediated through the PTEN/PI3K/AKT signaling pathway.

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