Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

Wei, Ping; Jiang, Wenyang; Chen, Wenshu; Sun, Wei; Fu, Xiangning

doi:10.7314/apjcp.2013.14.6.3613

Cited by 25 publications

(20 citation statements)

References 33 publications

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“…Overcoming radioresistance of hypoxia would effectively improve the efficacy of cancer radiation therapy (Brown, 2007). As a significant transcription factor closely correlated with hypoxia, HIF-1α has been focused for a long time (Liang et al, 2013;Ping et al, 2013;Zhang et al, 2013). Many investigations have revealed that the relationships between HIF-1α, VEGF and radioresistance resulted from hypoxic condition (Harada 2011) regarding HIF-1α, VEGF, HPSE-1 and CD31 as indirect indicators of tumor hypoxia and radioresistance.…”

Section: Discussionmentioning

confidence: 99%

Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

Zhang

Gang²,

Gao³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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Purpose: We aimed to detect the expression of HIF-1α, VEGF, HPSE-1 and CD31 in SKOV3 xenografts in nude mice treated with different doses of ionizing radiation, trying to explore the possible mechanism of hypoxia and radioresistance. Methods: Nude mice bearing SKOV3 xenografts were randomly divided into 4 groups: Group A (control group, no ionizing radiation), Group B (treated with low dose of ionizing radiation: 50cGy), Group C (treated with high dose of ionizing radiation: 300cGy), Group D ( combined ionizing radiation, treated with ionizing radiation from low dose to high dose : 50cGy first and 300cGy after 6h interval). The mRNA levels of HIF-1 and VEGF in each group were detected by real time polymerase chain reaction, while HPSE-1 expression was measured by ELISA. The microvessel density (MVD) and hypoxic cells were determined through immunohistochemical (IHC) staining of CD31 and HIF-1a. Results: Significant differences of HIF-1α mRNA level could be found among the 4 groups (F=74.164, P<0.001): Group C>Group A>Group D> Group B. The mRNA level of VEGF in Group C was significantly higher than in the other three groups (t=-5.267, P=0.000), while no significant difference was observed among Group A, B and D (t=1.528, 1.588; P=0.205, 0.222). In addition, the MVD was shown to be the highest in Group C (t=6.253, P=0.000), whereas the HPSE-1 level in Group A was lower than in Group B (t=14.066, P=0.000) and higher than in Group C (t=-21.919, P=0.000), and similar with Group D (t=-2.066, P=0.058). Through IHC staining of HIF-1a, the expression of hypoxic cells in Group A was (++), Group B was (+), Group C was (+++) and Group D was (+). Conclusion: Ionizing radiation with lowerdoses might improve tumor hypoxia through inhibiting the expression of HIF-1 and HPSE-1, whereas higherdoses worsen tumor hypoxic conditions by up-regulating HIF-1α, HPSE-1, VEGF and CD31 levels. A protocol of low-dose ionizing radiation followed by a high-dose irradiation might at least partly improve tumor hypoxia and enhance radiosensitivity.

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Section: Discussionmentioning

confidence: 99%

Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

Zhang

Gang²,

Gao³

et al. 2014

Asian Pacific Journal of Cancer Prevention

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“…Immunohistochemical (IHC) staining was performed to detect the expression of CYP2J2 in lung tissues using a Streptavidin/Peroxidase immunohistochemical kit (Fuzhou Maixin Biotechnology Co. Ltd, Fujian, China) according to the manufacturer's instruction [23]. The results were counted by two investigators in a double-blind fashion.…”

Section: Methodsmentioning

confidence: 99%

CYP2J2 and EETs Protect against Oxidative Stress and Apoptosisin Vivoandin VitroFollowing Lung Ischemia/Reperfusion

Chen

Zheng

Yang

et al. 2014

Cell Physiol Biochem

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Background: Cytochrome P450 epoxygenase 2J2 (CYP2J2) metabolizes arachidonic acids to epoxyeicosatrienoic acids (EETs). EETs exert various biological effects, including anti-inflammatory, anti-apoptotic, pro-proliferation, pro-angiogenesis, anti-oxidation, and anti-fibrosis effects. However, little is known about the role of CYP2J2 and EETs in lung ischemia/reperfusion injury. In this study, we examined the effects of exogenous EETs or CYP2J2 overexpression on lung ischemia/reperfusion injury in vivo and in vitro. Methods and Results: CYP2J2 gene was stably transfected into rat lungs via pcDNA3.1-CYP2J2 plasmid delivery, resulting in increased EETs levels in the serum and lung. A rat model of lung ischemia/reperfusion injury was developed by clamping the left lung hilum for 1 hour, followed by reperfusion for 2 hours. We found that CYP2J2 overexpression markedly decreased the levels of oxidative stress and cell apoptosis in lung tissues induced by ischemia/reperfusion. Moreover, we observed that exogenous EETs, or CYP2J2 overexpression, enhanced cell viability, decreased intracellular reactive oxygen species (ROS) generation, inhibited mitochondrial dysfunction, and attenuated several apoptotic signaling events in a human pulmonary artery endothelial cells (HPAECs)-based anoxia/reoxygenation model. These apoptotic events included activation of NADPH oxidase, collapse of mitochondrial transmembrane potential, and activation of pro-apoptotic proteins and caspase-3. These effects were mediated, at least partially, by the PI3K/Akt signaling pathway. Conclusion: These results reveal that CYP2J2 overexpression and exogenous EETs can protect against oxidative stress and apoptosis following lung ischemia/reperfusion in vivo and in vitro, suggesting that increasing the level of EETs may be a novel promising strategy to prevent and treat lung ischemia/reperfusion injury.

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“…We demonstrated significantly higher LOX mRNA expression levels in astrocytomas when compared to non-neoplastic brain tissue samples, most notably in GBM cases, as reported by others in different types of tumors [31][32][33][34][35]. Furthermore, higher BMP1…”

Section: Discussionsupporting

confidence: 64%

Expressão gênica da família das lisil oxidases e papel funcional de LOX em astrocitomas

Silva¹

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Expression and Significance of Hypoxia Inducible Factor-1α and Lysyl Oxidase in Non-small Cell Lung Cancer

Cited by 25 publications

References 33 publications

Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

Influence of Ionizing Radiation on Ovarian Carcinoma SKOV-3 Xenografts in Nude Mice under Hypoxic Conditions

CYP2J2 and EETs Protect against Oxidative Stress and Apoptosisin Vivoandin VitroFollowing Lung Ischemia/Reperfusion

Expressão gênica da família das lisil oxidases e papel funcional de LOX em astrocitomas

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