Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo

Luo, Xing-Mei; Xu, Bin; Zhou, Mingxi; Bao, Yang‐Yang; Zhou, Shui‐Hong; Fan, Jun; Zhang, Lu

doi:10.1371/journal.pone.0143306

Cited by 29 publications

(46 citation statements)

References 35 publications

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“…Glut-1 also affects cell proliferation and chemoradiotherapy sensitivity of head and neck squamous cell carcinoma, including laryngeal carcinoma13-18. Our previous studies suggested that Glut-1 may affect the proliferation, glucose uptake, chemosensitivity, and radiosensitivity [8,[13][14][15][16][17]. Although we found that the mechanism may be mediated through the PI3K/Akt pathway, the role of the activated PI3K/Akt pathway in this process was not significant.…”

Section: Introductioncontrasting

confidence: 72%

shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

Wang

Zhu

Zhou

et al. 2020

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Objective: Glut-1 is a key regulator in the process of glucose uptake. Previous studies have shown that Glut-1 affects autophagy. However, it is unclear whether there is a correlation between Glut-1 and autophagy in the progression of laryngeal carcinoma.This study was performed to investigate the role of Glut-1 in the development of laryngeal carcinoma.Methods: A stable HEp-2 cell model was constructed by Glut-1 and Beclin-1 shRNA lentiviral infection. The autophagosome was measured by transmission electron microscopy. Protein levels of LC3, ATG5, CyclinD1, Bcl-2, Caspase-3, and c-Myc were determined by Western blotting. CCK8 assay and Transwell assays were used to determine cell viability and migration rate of HEp-2 cells, respectively. Flow cytometry was performed to analyze the rate of apoptosis. Immunofluorescence was performed to determine the expression distribution of LC3. Results:Glut-1 knockdown significantly promoted autophagosome formation by upregulating the ratio of LC3-II/LC3-I as well as the role of rapamycin (RAP) andBeclin-1 overexpression on autophagy flux in HEp-2 cells. Glut-1 inhibition also reduced the viability of HEp-2 cells followed by the decreases in expression of cyclinD1 and c-Myc. In addition, Glut-1 depletion increased the number of apoptotic HEp-2 cells accompanied by activation of caspase-3 and downregulation of Bcl-2.Glut-1 knockdown also reduced the migration rate of HEp-2 cells by promoting the expression of N-cadherin and inhibiting the expression of E-cadherin. Beclin-1 consumption significantly reversed Gult-1 knockdown-mediated autophagy activation, resulting in promotion of both proliferation and migration and inhibition of apoptosis. Conclusions:Glut-1 knockdown-induced autophagy inhibits the proliferation and migration of HEp-2 cells, and promotes apoptosis of HEp-2 cells partly by regulating autophagy.

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Section: Introductioncontrasting

confidence: 72%

shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

Wang

Zhu

Zhou

et al. 2020

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“…Especially in HNSCC, the AKT signal transduction pathway is involved in the most important mechanisms of radioresistance: intrinsic radioresistance, tumor-cell proliferation, and hypoxia (3). Several studies have showed that suppressing AKT activity sensitizes cancer cells to irradiation (34)(35)(36). Therefore, our study provided evidence that TSA induced apoptosis in TSCC cells by upregulating miR-375 and subsequently suppressing the AKT cascade.…”

Section: Discussionsupporting

confidence: 51%

Trichostatin A increases radiosensitization of tongue squamous cell carcinoma via miR-375

et al. 2016

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Trichostatin A (TSA), a histone deacetylase inhibitor, is used as an anti-carcinogenic and radiosensitizing agent in various cancers. However, the role and mechanism underlying its radiosensitization of tongue squamous cell carcinoma (TSCC) remains unclear. Thus, in this study we aimed to confirm the promotion of miR‑375 expression by TSA, and to investigate the effects of TSA and miR‑375 in the radiosensitivity of TSCC cells. The results showed that TSA had significant radiosensitizing effects on TSCC cells and miR‑375 overexpression had effects similar to TSA in sensitizing these cells to radiotherapy. By contrast, miR‑375 knockdown attenuated apoptosis induced by radiation combined with TSA. Mechanistically, the histone acetylation status of the miR‑375 promoter region was increased by TSA, resulting in the upregulation of miR‑375, which led to a decline of PDK1 and phosphorylated AKT. Taken together, our data suggest that TSA increases the radiosensitization and apoptosis in TSCC cells at least partially via miR‑375, and TSA or miR‑375 in combination with radiotherapy may provide a valuable approach for the treatment of TSCC.

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“…Glucose is the main energy source for tumor cells and GLUT-1 is a key transporter of extracellular glucose [6,7,29]. GLUT-1 is overexpressed in many cancers, including laryngeal carcinoma, and is associated with their metastasis, drug resistance, and prognosis [6,7,[30][31][32][33][34][35][36]. We investigated the role of GLUT-1 in Tu212…”

Section: Discussionmentioning

confidence: 99%

Effect of Inhibition of GLUT1 Expression and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells under Hypoxic and Low-Glucose Conditions

Chen

Liu

Zhong

et al. 2020

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Background: Enhanced glucose uptake and autophagy are means by which cells adapt to stressful microenvironments. We investigated the roles of glucose transporter-1 (GLUT-1) and autophagy in laryngeal carcinoma stem cells under hypoxic and low-glucose conditions.Methods: CD133+ Tu212 laryngeal carcinoma stem cells were purified by magnetic-activated cell sorting and subjected to hypoxic and/or low-glucose conditions. Proliferation was evaluated using a cell-counting kit and a clone-formation assay, and migration was evaluated through a Transwell assay. Autophagy was assessed via transmission electron microscopy. GLUT-1 and beclin-1 expression were silenced using an shRNA and autophagy was manipulated using rapamycin, 3-MA, or chloroquine. Gene expression levels were evaluated by quantitative reverse transcription-polymerase chain reaction and protein concentrations were assessing via Western blotting.Results: Compared to CD133– stem cells, CD133+ cells showed increased proliferation and migration, and reduced apoptosis, under hypoxic or low-glucose conditions. They also showed increased expression of GLUT-1 and autophagy markers. Finally, GLUT-1 knockdown or autophagy inhibition reduced their proliferation and migration.Conclusions: Enhanced glucose uptake and autophagy maintain the functions of CD133+ laryngeal carcinoma stem cells under hypoxic and low-glucose conditions.

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Co-Inhibition of GLUT-1 Expression and the PI3K/Akt Signaling Pathway to Enhance the Radiosensitivity of Laryngeal Carcinoma Xenografts In Vivo

Cited by 29 publications

References 35 publications

shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

shRNA Glut-1 inhibits cell viability, apoptosis and migration of laryngeal carcinoma HEp-2 cells through regulating Beclin-1-mediated autophagy

Trichostatin A increases radiosensitization of tongue squamous cell carcinoma via miR-375

Effect of Inhibition of GLUT1 Expression and Autophagy Modulation on the Growth and Migration of Laryngeal Carcinoma Stem Cells under Hypoxic and Low-Glucose Conditions

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