Targeted Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibits Proliferation and Induces Apoptosis of Laryngeal Carcinoma Cells in vitro

Li, Rongrui; Wang, Riguang; Zhai, Raosheng; Dong, Zhen

doi:10.1177/030089161109700616

Cited by 11 publications

(11 citation statements)

References 38 publications

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“…Activated mTOR is frequently found in many human cancers [24]. In addition, blockade of mTOR was proved to be a new potential therapy for cancer treatment [25]. According to our results, ERBB2 exerted great influence on GC via the mTOR signaling pathway, and mTOR expression level was suppressed by miR-495.…”

Section: Discussionmentioning

confidence: 64%

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Han

Zhou

et al. 2018

Med Sci Monit

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BackgroundIn recent years, the incidence of gastric cancer (GC) has been increasing worldwide. Emerging evidence shows that microRNAs (miRs) may be involved in the pathogenesis of GC. Thus, this study explored the mediatory role of miR-495 in GC chemosensitivity, and investigated the mechanism by which it affects the biological behaviors of GC cells via the mTOR signaling pathway.Material/MethodsAfter GC and paracancerous tissue collection, the positive rate of ERBB2 and mTOR was evaluated by immunohistochemistry. Subsequently, the expression of miR-495, ERBB2, and mTOR was determined by RT-qPCR and Western blot analysis. Next, the targeting relationship between miR-495 and ERBB2 was confirmed by dual-luciferase reporter gene assay. In addition, chemosensitivity and proliferation were detected by MTT assay and apoptosis was assessed by flow cytometry.ResultsWe found higher positive rates of ERBB2 and mTOR and decreased expression of miR-495 in GC tissues and showed that ERBB2 is the target gene of miR-495. Furthermore, we determined that overexpression of miR-495 and silencing of ERBB2 enhanced GC cell chemosensitivity and apoptosis, but inhibited GC cell proliferation. We also found that the effect of miR-495 inhibition was lost when ERBB2 was suppressed.ConclusionsThe key findings of our study demonstrate that the miR-495 exerts promotive effects on GC chemosensitivity via inactivation of the mTOR signaling pathway by suppressing ERBB2. The study provides reliable evidence supporting the use of miR-495 as a novel potential target in the chemotherapy of GC.

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Section: Discussionmentioning

confidence: 64%

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Han

Zhou

et al. 2018

Med Sci Monit

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“…The mTORC1, consisted of mTOR, mLST8 and raptor, is sensitive to rapamycin. The major substrates of mTORC1 are S6 kinase and 4E-BP through which mTORC1 regulates protein translation, cell proliferation, apoptosis and autophagy [5,6,7,8]. The mTORC2, containing mTOR, mLST8, rictor, mSIN1, and PRR5, is insensitive to rapamycin.…”

Section: Introductionmentioning

confidence: 99%

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

Zhang

Shan

Liang

et al. 2014

Biochemical and Biophysical Research Communications

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Mammalian target of rapamycin (mTOR) is a critical regulator of protein synthesis, cell proliferation and energy metabolism. As constitutive knockout of Mtor leads to embryonic lethality, the in vivo function of mTOR in perinatal development and postnatal growth of heart is not well defined. In this study, we established a muscle-specific mTOR conditional knockout mouse model (mTOR-mKO) by crossing MCK-Cre and Mtorflox/flox mice. Although the mTOR-mKO mice survived embryonic and perinatal development, they exhibited severe postnatal growth retardation, cardiac muscle pathology and premature death. At the cellular level, the cardiac muscle of mTOR-mKO mice had fewer cardiomyocytes due to apoptosis and necrosis, leading to dilated cardiomyopathy. At the molecular level, the cardiac muscle of mTOR-mKO mice expressed lower levels of fatty acid oxidation and glycolysis related genes compared to the WT littermates. In addition, the mTOR-mKO cardiac muscle had reduced Myh6 but elevated Myh7 expression, indicating cardiac muscle degeneration. Furthermore, deletion of Mtor dramatically decreased the phosphorylation of S6 and AKT, two key targets downstream of mTORC1 and mTORC2 mediating the normal function of mTOR. These results demonstrate that mTOR is essential for cardiomyocyte survival and cardiac muscle function.

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“…The mammalian target of rapamycin (mTOR), an atypical serine/threonine (S/T) protein kinase, plays a central role in controlling cell growth, proliferation and metabolism (19,20). Activation of the mTOR pathway was noted in melanoma (21), squamous cell cancers (22), adenocarcinomas (23), colorectal cancers (24) and lymphomas (25).…”

Section: Introductionmentioning

confidence: 99%

Curcumin enhances the response of non-Hodgkin’s lymphoma cells to ionizing radiation through further induction of cell cycle arrest at the G2/M phase and inhibition of mTOR phosphorylation

Qiao¹,

Jiang²,

Li³

2012

Oncology Reports

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Abstract. It is crucial to enhance tumor radiosensitivity for the purpose of both lowering the dose of ionizing radiation (IR) and achieving higher antitumor efficacy. We identified curcumin as a radiosensitizer to enhance non-Hodgkin's lymphoma (NHL) cell response to IR in vitro and further investigated the mechanism mediating this effect. We treated Namalwa, Ramos and Raji cell lines with vehicle, curcumin, IR and curcumin-IR. Cell viability and cell cycle distribution were determined to ascertain the radiosensitization effect of curcumin. DNA damage-related proteins, cell cycle regulatory proteins, phosphorylation of mammalian target of rapamycin (mTOR) and the nuclear translocation of the downstream nuclear factor-κB (NF-κB) target were examined by western blotting. Treatment with curcumin led to decreased viability of all three types of NHL cells and had a profound radiosensitization effect. Pre-treatment with curcumin at a low concentration of 2 µmol/l increased IR-induced G2/M arrest in the cell cycle and increased the expression of cyclin-dependent kinase inhibitors, p21 cip1 and p53. However, this effect was blocked when NHL cells were pre-treated with 10 µmol/l of KU55933, a specific inhibitor of ataxia-telangiectasia-mutated (ATM). Pre-treatment with curcumin inhibited the phosphorylation of mTOR and the nuclear translocation of the downstream NF-κB target induced by IR. Curcumin enhanced the cell response to IR in NHL mediated through the induction of G2/M phase arrest and the inhibition of both a constitutive and IR-induced activation of the mTOR-NF-κB pathway. This offers great potential for curcumin to be used in conjunction with radiotherapy for NHL in order to increase the efficiency of the treatment.

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Targeted Inhibition of Mammalian Target of Rapamycin (mTOR) Signaling Pathway Inhibits Proliferation and Induces Apoptosis of Laryngeal Carcinoma Cells in vitro

Cited by 11 publications

References 38 publications

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

MicroRNA-495 Confers Increased Sensitivity to Chemotherapeutic Agents in Gastric Cancer via the Mammalian Target of Rapamycin (mTOR) Signaling Pathway by Interacting with Human Epidermal Growth Factor Receptor 2 (ERBB2)

Mammalian target of rapamycin is essential for cardiomyocyte survival and heart development in mice

Curcumin enhances the response of non-Hodgkin’s lymphoma cells to ionizing radiation through further induction of cell cycle arrest at the G2/M phase and inhibition of mTOR phosphorylation

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