PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond

Fattahi, Sadegh; Amjadi‐Moheb, Fatemeh; Tabaripour, Rabeeh; Ashrafi, G. Hossein; Akhavan‐Niaki, Haleh

doi:10.1016/j.lfs.2020.118513

Cited by 235 publications

(164 citation statements)

References 215 publications

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“…ROS inhibition can activate molecular pathways involved in cancer progression and phosphoinositide 3-kinase (PI3K)/protein kinase-B (Akt) is one of them. It has been reported that activation of PI3K/Akt axis not only promotes proliferation and metastasis of cancer cells [122][123][124][125], but also triggers chemoresistance [126][127][128][129]. Therefore, it is important to reveal the role of this molecular pathway in CP resistance of cancer cells and providing prospects for its targeting.…”

Section: Cisplatin Resistancementioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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The failure of chemotherapy is a major challenge nowadays, and in order to ensure effective treatment of cancer patients, it is of great importance to reveal the molecular pathways and mechanisms involved in chemoresistance. Cisplatin (CP) is a platinum-containing drug with anti-tumor activity against different cancers in both pre-clinical and clinical studies. However, drug resistance has restricted its potential in the treatment of cancer patients. CP can promote levels of free radicals, particularly reactive oxygen species (ROS) to induce cell death. Due to the double-edged sword role of ROS in cancer as a pro-survival or pro-death mechanism, ROS can result in CP resistance. In the present review, association of ROS with CP sensitivity/resistance is discussed, and in particular, how molecular pathways, both upstream and downstream targets, can affect the response of cancer cells to CP chemotherapy. Furthermore, anti-tumor compounds, such as curcumin, emodin, chloroquine that regulate ROS and related molecular pathways in increasing CP sensitivity are described. Nanoparticles can provide co-delivery of CP with anti-tumor agents and by mediating photodynamic therapy, and induce ROS overgeneration to trigger CP sensitivity. Genetic tools, such as small interfering RNA (siRNA) can down-regulate molecular pathways such as HIF-1α and Nrf2 to promote ROS levels, leading to CP sensitivity. Considering the relationship between ROS and CP chemotherapy, and translating these findings to clinic can pave the way for effective treatment of cancer patients.

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Section: Cisplatin Resistancementioning

confidence: 99%

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

et al. 2021

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“…The PI3K/AKT/mTOR signalling pathway plays an important role in numerous diseases, including cancer. This pathway controls several key cellular processes responsible for cellular homeostasis, while aberrant activation of the pathway has been observed in human cancers 51,52 . In the skin, this pathway is crucial for skin development and homeostasis 53 .…”

Section: Discussionmentioning

confidence: 99%

SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling

Liu

Zhu

et al. 2021

Cell Proliferation

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“…CTAB can increase the expression of proapoptotic Bax and downregulate the expression of antiapoptotic Bcl-2, thereby increasing mitochondrial permeability. The PI3K/AKT pathway is a widely studied intracellular signaling pathway that plays an indispensable role in all malignant phenotypes (such as tumorigenesis, cancer cell proliferation, survival, migration, and chemoresistance) (33,34). According to reports, dysregulation of the PI3K/AKT pathway also plays a vital role in the occurrence and development of OS (35).…”

Section: Discussionmentioning

confidence: 99%

The inhibitory effect of CTAB on human osteosarcoma through the PI3K/AKT signaling pathway

Lin

Zhu

2021

Int J Oncol

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Osteosarcoma (OS) metastasis and recurrence and multidrug resistance are three major obstacles in the clinic. New highly effective and low toxicity drugs for osteosarcoma are needed. The antitumoral efficacy of cetrimonium bromide (CTAB), a quaternary ammonium compound, is gradually being investigated. The aim of the present study was to investigate the effects of CTAB on OS cells and the underlying mechanisms. CTAB inhibited the proliferation of osteosarcoma cells in a concentration-and time-dependent manner, resulting in cell cycle arrest in G1 phase. CTAB also suppressed the migration and invasion of HOS and MG63 cells at a low concentration without inhibiting the growth of human osteoblasts. Moreover, CTAB promoted caspase-mediated apoptosis of osteosarcoma cells through the PI3K/AKT cascade, and this effect was accompanied by obvious mitochondrial toxicity. In vivo, CTAB inhibited OS proliferation without inducing organ toxicity. In conclusion, this study reveals that CTAB has an inhibitory effect on OS by suppressing proliferation and metastasis and inducing apoptosis through the PI3K/AKT signaling pathway and identifies CTAB as a potential therapeutic drug.

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PI3K/AKT/mTOR signaling in gastric cancer: Epigenetics and beyond

Cited by 235 publications

References 215 publications

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

Elucidating Role of Reactive Oxygen Species (ROS) in Cisplatin Chemotherapy: A Focus on Molecular Pathways and Possible Therapeutic Strategies

SETD2 epidermal deficiency promotes cutaneous wound healing via activation of AKT/mTOR Signalling

The inhibitory effect of CTAB on human osteosarcoma through the PI3K/AKT signaling pathway

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