Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review)

Shi, Xiang; Wang, Jingjing; Yu, Lei; Cong, Caofan; Tan, Dailin; Zhou, Xianrong

doi:10.3892/mmr.2019.10121

Cited by 138 publications

(133 citation statements)

References 90 publications

(98 reference statements)

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“…The PI3K/Akt signaling pathway is a pathway essential for cell survival, growth and proliferation (Shi et al, 2019). This pathway is activated by the binding of ligands (such as hormones, growth factors and extracellular matrix components) with receptor tyrosine kinase (RTK) resulting in dimerization and autophosphorylation of tyrosine residues in the cytoplasmic domain.…”

Section: The Phosphatidylinositol 3-kinase (Pi3k)/ Protein Kinase B (mentioning

confidence: 99%

The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas

Wong

Chin

2020

Front. Pharmacol.

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Lithium, the lightest natural-occurring alkali metal with an atomic number of three, stabilizes the mood to prevent episodes of acute manic and depression. Multiple lines of evidence point to lithium as an anti-suicidal, anti-viral, anti-cancer, immunomodulatory, neuroprotective and osteoprotective agent. This review article provides a comprehensive review of studies investigating the bone-enhancing effects of lithium and its possible underlying molecular mechanisms. Most of the animal experimental studies reported the beneficial effects of lithium in defective bones but not in healthy bones. In humans, the effects of lithium on bones remain heterogeneous. Mechanistically, lithium promotes osteoblastic activities by activating canonical Wingless (Wnt)/beta (b)-catenin, phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) and bone morphogenetic protein-2 (BMP-2) transduction pathways but suppresses osteoclastic activities by inhibiting the receptor activator of nuclear factor-kappa B (RANK)/receptor activator of nuclear factor-kappa B ligand (RANKL)/osteoprotegerin (OPG) system, nuclear factorkappa B (NF-kB), mitogen-activated protein kinase (MAPK), and calcium signaling cascades. In conclusion, lithium confers protection to the skeleton but its clinical utility awaits further validation from human clinical trials.

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Section: The Phosphatidylinositol 3-kinase (Pi3k)/ Protein Kinase B (mentioning

confidence: 99%

The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas

Wong

Chin

2020

Front. Pharmacol.

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“…The PI3K/Akt signaling pathway, a critical second messenger pathway downstream of the TCR signaling apparatus, is involved in the regulation of multiple cellular physiological processes through its regulation of downstream corresponding effector molecules such as p21, which plays an important role in cell cycle, growth and proliferation 21,22 . Interestingly, we discovered that DCAAA treatment resulted in the downregulation of PI3K, phosphorylated PDK1 and phosphorylated Akt and arrested cell cycle by an increase in p21 and decrease in CDK2 expression.…”

Section: Discussionmentioning

confidence: 92%

Combination of N, N′‐dicyclohexyl‐N‐arachidonic acylurea and tacrolimus prolongs cardiac allograft survival in mice

Qin

et al. 2020

Immunol Cell Biol

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Current immunosuppressive agents for organ transplantation are not ideal because of their strong toxicity and adverse effects. Hence, there is an urgent need to develop novel immunosuppressive agents. The compound N, N 0dicyclohexyl-N-arachidonic acylurea (DCAAA) is a novel highly unsaturated fatty acid from the traditional Chinese medicinal plant Radix Isatidis. In this study, we systematically investigated the toxicity, immunosuppressive effect and mechanisms underlying the activity of DCAAA. The toxicity tests showed that DCAAA treatment did not lead to red blood cell hemolysis and did not affect the liver and kidney functions in mice. The lymphocyte transformation test showed that DCAAA treatment inhibited lymphocyte proliferation in a dosedependent manner. An in vivo cardiac allotransplantation experiment showed that DCAAA treatment could suppress the immune rejection and significantly prolong the survival of cardiac allografts in recipient mice by reducing the proportion of CD4 + T cells in the spleen and grafts, concentration of interferon-c in the supernatant and serum and infiltration of inflammatory cells into the grafts. Moreover, a combination treatment with DCAAA and tacrolimus had a synergistic effect in preventing acute rejection of heart transplants. In vitro molecular biology experiments showed that DCAAA treatment inhibited activation of the T-cell receptor-mediated phosphoinostide 3-kinase-protein kinase B pathway, thereby arresting cell cycle transition from the G 1 to the S phase, and inhibiting lymphocyte proliferation. Overall, our study reveals a novel, low-toxicity immunosuppressive agent that has the potential to reduce the toxic side effects of existing immunosuppressive agents when used in combination with them.

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“…The involvement of PI3K/AKT signalling in glioma is known in terms of regulating the ability of cells to divide, migrate, invade and undergo angiogenesis . Oncogenesis caused by FGFR1 was earlier shown to be associated with PI3K/AKT signalling pathway .…”

Section: Discussionmentioning

confidence: 99%

MiR‐3116 sensitizes glioma cells to temozolomide by targeting FGFR1 and regulating the FGFR1/PI3K/AKT pathway

Kong

Cao

et al. 2020

J Cellular Molecular Medi

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| 4677 wileyonlinelibrary.com/journal/jcmm | INTRODUC TI ONGlioma accounts for 30% of brain tumours and 80% malignancies making it a ubiquitous malignancy of the brain. 1,2 While there have been developments to address this condition, the median survival is 12-14 months for the high-grade disease causing the prognosis. 3 One approach is the use of chemotherapy (temozolomide: TMZ) plus surgery and radiotherapy. This approach, however, is challenged by TMZ resistance (inherent and acquired). 4,5 This calls for the addressing of this condition to boost the responses of the malignancy to TMZ. MicroRNAs (MiRNAs) are the small endogenous non-coding RNAs that could inhibit translation or degrade mRNA by base-pairing to the 3′-untranslated region (UTR) of targets to result in the inactivation of the latter. 6,7 Research has shown that miRNAs are oncogenes or tumour suppressors by targeting the cell cycle, cell division, apoptosis and angiogenesis in numerous human cancers. 8 There is also proof of the functioning of miRNAs in the resistance to chemotherapeutic AbstractGlioma is a brain tumour that is often diagnosed, and temozolomide (TMZ) is a common chemotherapeutic drug used in glioma. Yet, resistance to TMZ is a chief hurdle towards curing the malignancy. The current work explores the pathways and involvement of miR-3116 in the TMZ resistance. miR-3116 and FGFR1 mRNA were quantified by real-time PCR in malignant samples and cell lines. Appropriate assays were designed for apoptosis, viability, the ability to form colonies and reporter assays to study the effects of the miR-3116 or FGFR1. The involvement of PI3K/AKT signalling was assessed using Western blotting. Tumorigenesis was evaluated in an appropriate xenograft mouse model in vivo. This work revealed that the levels of miR-3116 dipped in samples resistant to TMZ, while increased miR-3116 caused an inhibition of the tumour features mentioned above to hence augment TMZ sensitivity. miR-3116 was found to target FGFR1. When FGFR1 was overexpressed, resistance to TMZ was augmented and reversed the sensitivity caused by miR-3116. Our findings further confirmed PI3K/AKT signalling pathway is involved in this action. In conclusion, miR-3116 sensitizes glioma cells to TMZ through FGFR1 downregulation and the PI3K/ AKT pathway inactivation. Our results provide a strategy to overcome TMZ resistance in glioma treatment. K E Y W O R D Sdrug resistance, FGFR1, FGFR1/PI3K/AKT, miR-3116, temozolomide

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Research progress on the PI3K/AKT signaling pathway in gynecological cancer (Review)

Cited by 138 publications

References 90 publications

The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas

The Skeletal-Protecting Action and Mechanisms of Action for Mood-Stabilizing Drug Lithium Chloride: Current Evidence and Future Potential Research Areas

Combination of N, N′‐dicyclohexyl‐N‐arachidonic acylurea and tacrolimus prolongs cardiac allograft survival in mice

MiR‐3116 sensitizes glioma cells to temozolomide by targeting FGFR1 and regulating the FGFR1/PI3K/AKT pathway

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