HIF-1α effects on angiogenic potential in human small cell lung carcinoma

Wan, Jun; Chai, Hua; Yu, Zhengping; Ge, Wei; Kang, Ningning; Xia, Wanli; Cao, Yun

doi:10.1186/1756-9966-30-77

Cited by 69 publications

(66 citation statements)

References 48 publications

(53 reference statements)

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“…Consistent with results from previous studies, the present results demonstrated that in A549 cells, HIF-1α mRNA and protein were expressed at low levels under normoxic conditions; however, mRNA and protein levels increased markedly under hypoxia (13,15). Previous evidence has suggested that HIF-1α is important in the regulation of cell growth and development, as well as invasion of AC (11,16). It was therefore hypothesized that the downregulation of HIF-1α was likely to lead to growth inhibition of AC.…”

Section: Discussionsupporting

confidence: 81%

“…Evidence suggests that HIF-1α is widely expressed in NSCLC tissue, and is associated with the expression of numerous biological factors involved in NSCLC pathogenesis, including vascular endothelial growth factor, platelet-derived endothelial cell growth factor and basic fibroblastic growth factor (8,11,(13)(14)(15)(16). In addition, high levels of HIF-1α are also associated with a poor prognosis, independent of routinely used clinicopathological variables.…”

Section: Introductionmentioning

confidence: 99%

“…Overexpression of HIF-1α has been detected in >70% of solid tumors. While upregulation or activation of HIF-1α promotes tumor growth, downregulation or loss of HIF-1α activity has been demonstrated to markedly decrease tumor growth, vascularization and energy metabolism (8)(9)(10)(11). The suppression of HIF-1α expression by RNA interference (RNAi) has been shown to be an effective method of cancer therapy (12).…”

Section: Introductionmentioning

confidence: 99%

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HIF-1α silencing suppresses growth of lung adenocarcinoma A549 cells through induction of apoptosis

Liao

Wang

Huang

et al. 2014

Molecular Medicine Reports

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Abstract. Lung adenocarcinoma (AC) is one of the most deadly malignancies. The disease has a low five-year survival rate; therefore, the identification of novel therapeutic agents is required. This study aimed to investigate the effect of small interfering RNA (siRNA) targeting hypoxia-inducible factor 1α (HIF-1α) on the growth of AC A549 cells. A549 cells were transfected with various concentrations of HIF-1α or control siRNA, and the effect on HIF-1α expression was analyzed using quantitative polymerase chain reaction and western blot analysis. The effects of HIF-1α siRNA on growth inhibition and apoptosis were then assessed using standard methods. HIF-1α siRNA treatment significantly reduced HIF-1α mRNA and protein expression in A549 cells. Furthermore, the downregulation of HIF-1α expression inhibited the growth of A549 cells and induced apoptosis of A549 cells by upregulating caspase-3 expression. The present in vitro study demonstrates that the downregulation of HIF-1α is capable of suppressing AC A549 cell growth, through the induction of apoptosis. This suggests that HIF-1α inhibition may represent a promising strategy for the treatment of AC.

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Section: Discussionsupporting

confidence: 81%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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HIF-1α silencing suppresses growth of lung adenocarcinoma A549 cells through induction of apoptosis

Liao

Wang

Huang

et al. 2014

Molecular Medicine Reports

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“…HIF is a key regulator of cellular responses to hypoxia (12). It targets the genes involved in tumour cell energy metabolism, angiogenesis, tumour metastasis, ion metabolism and catecholamine metabolism, thereby influencing the expression of proteins, including erythropoietin, vascular endothelial growth factor, GLUT-1, glyceraldehyde 3-phosphate dehydrogenase, inducible nitric oxide synthase, insulin-like growth factor-2, tyrosine hydroxylase and glycolytic enzymes (27). HIF-1α and GLUT-1 are the intrinsic hypoxia markers that have been studied the most in various tumours (13)(14)(15)(16)(17)(18).…”

Section: Discussionmentioning

confidence: 99%

Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Chen

Jianying

et al. 2012

Oncology Letters

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Abstract. Malignant cells show increased glucose uptake in vitro and in vivo. This process is considered to be mediated by glucose transporters (GLUTs). Hypoxia-inducible factor-1α (HIF-1α) may upregulate GLUT-1 expression. Little is known about the correlation between HIF-1α and GLUT-1 expression in laryngeal carcinoma. The current study investigated this correlation immunohistochemically, according to various clinical and pathological features, in 49 paraffin-embedded archival tissue blocks from patients with laryngeal squamous cell carcinoma. HIF-1α and GLUT-1 expression was detected in 63.3 (31/49) and 55.1% (27/49) of the tumour samples, respectively. HIF-1α expression was significantly correlated with lymph node classification (P= 0.018), recurrence (P= 0.02) and metastasis (P= 0.031). GLUT-1A expression was significantly associated with recurrence (P=0.02) and metastasis (P=0.01). Univariate analyses revealed that HIF-1α (χ 2 =8.2; P=0.004) and GLUT-1 expression (χ 2 =9.0; P=0.003) were significantly associated with a poorer survival rate. In a multivariate analysis, GLUT-1 expression (P=0.006) was a significant predictor of poor survival rate, as well as the primary tumour site, lymph node invasion and distant metastasis. Based on Spearman's analysis, GLUT-1 expression and phosphatidylinositol 3-kinase (PI3K) expression were significantly correlated (r=0.504; P=0.000). This is the first study to demonstrate a significant correlation between GLUT-1 and HIF-1α expression in laryngeal carcinoma and to show increased GLUT-1 expression as an independent survival rate predictor. These results suggest that GLUT-1 is a potential new therapeutic target for laryngeal carcinoma.

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“…Wan et al demonstrated that HIF-1a promotes growth and angiogenesis in SCLC by upregulating the expression of angiogenic genes and proposed HIF-1a as a potential target in the treatment of SCLC (26). Interestingly, the blockade of c-kit inducible HIF-1a by imatinib has been shown to downregulate VEGF expression in SCLC cell lines (27).…”

Section: Angiogenesis In Sclcmentioning

confidence: 99%

Targeting angiogenesis in small cell lung cancer

Stratigos

Matikas

Voutsina

et al. 2016

Transl. Lung Cancer Res.

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Small cell lung cancer (SCLC) is a highly aggressive and lethal malignancy. Despite high initial response rates to systemic chemotherapy, the disease eventually relapses; further treatment only modestly improves outcomes and overall survival (OS) for patients with extensive stage disease is less than one year.Little progress has been made during the past decades, with no new drugs approved. Consequently, the development of novel strategies is an unmet need. The inhibition of angiogenesis, a defining characteristic of cancer, has demonstrated modest efficacy in several human malignancies, including non-small cell lung cancer (NSCLC). However, results from clinical trials in SCLC have been disappointing, and no anti-angiogenic agent has received regulatory approval due to lack of clinical efficacy. The elucidation of underlying mechanisms responsible for tumor resistance to angiogenic therapy and the simultaneous blockade of multiple elements that play a role in angiogenesis need to be further explored.

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HIF-1α effects on angiogenic potential in human small cell lung carcinoma

Cited by 69 publications

References 48 publications

HIF-1α silencing suppresses growth of lung adenocarcinoma A549 cells through induction of apoptosis

HIF-1α silencing suppresses growth of lung adenocarcinoma A549 cells through induction of apoptosis

Expression and significance of hypoxia-inducible factor-1α and glucose transporter-1 in laryngeal carcinoma

Targeting angiogenesis in small cell lung cancer

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