Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Sonis, Stephen T.; Mendes, Rui Amaral

doi:10.1111/jop.12436

Cited by 11 publications

(11 citation statements)

References 40 publications

(52 reference statements)

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“…Our results showed that PI3K inhibitor treatment attenuates the inflammatory cell infiltration in experimental AAAs. The Wortmannin can reduce influx of the CD3 + T cells and CD31 + blood vessels as previous described 26 , 29 . In our study, PI3K inhibition treatment significantly reduced aortic macrophage infiltration while suppressing AAA formation and progression, as the CD68 + macrophages in Wortmannin group is less than the Vehicle one.…”

Section: Discussionsupporting

confidence: 59%

“…Early findings confirm and extend prior observations regarding wortmannin in the treatment of cancer 24 , 25 . As recently document indicates a potential important role of PI3K/AKT pathway in inflammation 26 , 27 , it is rational to question whether PI3K inhibitor could limits the progression of AAA. Our results demonstrate for the first time that Wortmannin, a prototype and classical PI3K inhibitor, suppresses PI3K/AKT pathway and prevents the formation and progression of experimental abdominal aortic aneurysm in rats.…”

Section: Discussionmentioning

confidence: 99%

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Inhibition of Phosphatidylinositol 3-kinease suppresses formation and progression of experimental abdominal aortic aneurysms

Liu

Huang

et al. 2017

Sci Rep

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Accumulating evidence suggests an important role of Phosphatidylinositol 3-kinease (PI3K) pathway in inflammatory cells infiltration. Given the essential role of inflammatory cells infiltration during the formation and progression of abdominal aortic aneurysm (AAA), to investigate the possibility of preventing AAA formation and progression via targeting PI3K is anticipated. Here, experimental AAAs was created in rats by transient intraluminal porcine pancreatic elastase (PPE) infusion into the infrarenal aorta firstly. AAAs rats were administrated with vehicle or Wortmannin during the period of day 0 to day 28 after PPE infusion. The aortic diameter of rats treated with Wortmannin was significantly smaller than those treated with vehicle. Meanwhile, Elastin destruction score and SMC destruction score were significantly decreased in rats treated with Wortmannin. Furthermore, histological analysis revealed infiltration of inflammatory cells were significantly reduced in rats treated with Wortmannin. Finally, the mRNA expression of PI3K and protein expression of pAKT in human abdominal aneurismal aorta tissues was elevated as compare to normal aorta. Our study revealed that PI3K inhibitor suppresses experimental AAAs formation and progression, through mechanisms likely related to impairing inflammation cells infiltration and median elastin degradation. These findings indicated that PI3K inhibitor may hold substantial translation value for AAA diseases.

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Section: Discussionsupporting

confidence: 59%

Section: Discussionmentioning

confidence: 99%

Inhibition of Phosphatidylinositol 3-kinease suppresses formation and progression of experimental abdominal aortic aneurysms

Liu

Huang

et al. 2017

Sci Rep

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“…Therefore, it is believed that Genipin inhibits OSCC cells growth and improves the autophagy through suppressing PI3K/Akt/mTOR signaling pathway, and PI3K/Akt/mTOR pathway is an attractive target for the treatment of OSCC. 39 Conclusively, this study showed that Genipin inhibited the cells' viability, induced apoptosis, and promoted autophagy in OSCC, and its mechanism might be related to the inhibition of PI3K/Akt/mTOR signaling pathway. It provided a new candidate for OSCC drug treatment.…”

Section: Discussionmentioning

confidence: 71%

<p>Genipin Induces Autophagy and Suppresses Cell Growth of Oral Squamous Cell Carcinoma via PI3K/AKT/MTOR Pathway</p>

Wei

Liu

et al. 2020

DDDT

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Background: Oral squamous cell carcinoma (OSCC) is a common malignant tumor of the head and neck, and it accounts for more than 90% of oral cancer. Due to high mortality, limitations of traditional treatment and many complications, new treatment methods are urgently needed. This study aimed to look into the effect of new potential anti-tumor drug, genipin, on OSCC treatment. Methods: In vitro, CCK-8, colony formation, and flow cytometry were used to detect the effect of genipin on SCC-9 and SCC-15 cell lines. Immunofluorescence, real-time PCR, and Western blotting were used to investigate its mechanism. Xenograft tumor model was used to explore the role of genipin in vivo. Results: We found that genipin suppressed cell growth and induced apoptosis in vitro. In addition, the expression of p62 was down-regulated while Beclin1 and LC3II were up-regulated in SCC-25 and SCC-9 cells. 3-methyladenine (3-MA) significantly decreased LC3 (LC3II) + puncta, but genipin rescuect 3d this reduction. Furthermore, genipin also reduced the expression of p-PI3K, p-AKT, and p-mTOR. In vivo experiment showed that genipin significantly curbed the tumor size and weight. The positive expression of Ki67 protein and number of apoptotic cells were increased. Conclusion: Conclusively, this study implicated that genipin suppresses cell proliferation and stimulated apoptosis, and is the first exploration showing that genipin induces OSCC cell autophagy via PI3K/AKT/mTOR pathway inhibition.

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“…The gain of function mutations in the upstream gene, phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha (PIK3CA), induces the oncogenic transformation of the AKT/mTOR signaling, leading to metabolic reprogramming in cells and subsequently causing OC development [101,102]. In 2016, Sonis and Mendes also postulated that the AKT/mTOR pathway drove the transformation of oral cells from benign to the malignant stage [103].…”

Section: Role Of Akt/mtor Pathway In Different Cellular Processes Of mentioning

confidence: 99%

Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials

Harsha

Banik

Ang

et al. 2020

IJMS

154

110

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Oral cancer (OC) is a devastating disease that takes the lives of lots of people globally every year. The current spectrum of treatment modalities does not meet the needs of the patients. The disease heterogeneity demands personalized medicine or targeted therapies. Therefore, there is an urgent need to identify potential targets for the treatment of OC. Abundant evidence has suggested that the components of the protein kinase B (AKT)/ mammalian target of rapamycin (mTOR) pathway are intrinsic factors for carcinogenesis. The AKT protein is central to the proliferation and survival of normal and cancer cells, and its downstream protein, mTOR, also plays an indispensable role in the cellular processes. The wide involvement of the AKT/mTOR pathway has been noted in oral squamous cell carcinoma (OSCC). This axis significantly regulates the various hallmarks of cancer, like proliferation, survival, angiogenesis, invasion, metastasis, autophagy, and epithelial-to-mesenchymal transition (EMT). Activated AKT/mTOR signaling is also associated with circadian signaling, chemoresistance and radio-resistance in OC cells. Several miRNAs, circRNAs and lncRNAs also modulate this pathway. The association of this axis with the process of tumorigenesis has culminated in the identification of its specific inhibitors for the prevention and treatment of OC. In this review, we discussed the significance of AKT/mTOR signaling in OC and its potential as a therapeutic target for the management of OC. This article also provided an update on several AKT/mTOR inhibitors that emerged as promising candidates for therapeutic interventions against OC/head and neck cancer (HNC) in clinical studies.

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Could the PI3K canonical pathway be a common link between chronic inflammatory conditions and oral carcinogenesis?

Cited by 11 publications

References 40 publications

Inhibition of Phosphatidylinositol 3-kinease suppresses formation and progression of experimental abdominal aortic aneurysms

Inhibition of Phosphatidylinositol 3-kinease suppresses formation and progression of experimental abdominal aortic aneurysms

<p>Genipin Induces Autophagy and Suppresses Cell Growth of Oral Squamous Cell Carcinoma via PI3K/AKT/MTOR Pathway</p>

Targeting AKT/mTOR in Oral Cancer: Mechanisms and Advances in Clinical Trials

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