Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1α expression through activation of AKT and P70S6K1 in human ovarian cancer cells

Liu, Lingzhi; Hu, Xiaowen; Xia, Chang; He, Jie; Zhou, Qiong; Shi, Xianglin; Fang, Jing; Jiang, Bing-Hua

doi:10.1016/j.freeradbiomed.2006.08.003

Cited by 198 publications

(136 citation statements)

References 66 publications

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“…In ovarian cancer, the PI3K signaling pathway plays an important role in proliferation, antiapoptosis, and tumorigenesis [46]. Increasing evidence suggests the involvement of PI3K/AKT in cell migration, invasion, and metastasis in normal and neoplastic tissues, including ovarian cancer [28,47,48].…”

Section: Discussionmentioning

confidence: 99%

“…To investigate the correlation between FSH, survivin, and HIF-1α, we stimulated SKOV-3 cells with 40 mIU/mL FSH for 0, 8,16,24,48, or 72 h. Western blot analysis showed that the survivin and HIF-1α expression levels increased gradually over time in SKOV-3 cells, peaked at 24 h, and then declined slightly, indicating a time-dependent correlation (Figure 2A and 2B).…”

Section: Fsh Stimulation Of Survivin and Hif-1α Expression In Skov-3 mentioning

confidence: 95%

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Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

et al. 2008

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There is evidence to suggest that follicle-stimulating hormone (FSH) can facilitate the neovascularization of ovarian cancers by increasing vascular endothelial growth factor (VEGF) expression in cancer cells, although the underlying molecular mechanism of this process is not well known. Therefore, we investigated the effect of FSH on VEGF expression in the ovarian cancer cell lines SKOV-3 and ES-2. Treatment with FSH significantly increased VEGF expression in a dose-and time-dependent manner. In addition, FSH treatment enhanced the expression of survivin and hypoxiainducible factor-1 (HIF-1α). Knockdown of survivin or HIF-1α suppressed VEGF expression, but only knockdown of survivin inhibited FSH-stimulated VEGF expression. Pretreatment with LY294002, a phosphoinositide 3-kinase (PI3K)/AKT inhibitor, neutralized the enhanced expression of survivin induced by FSH, but treatment with U0126, a mitogen-activated protein kinase/extracellular signal-regulated kinase inhibitor, had no such effect. We further showed that ovarian serous cystadenocarcinoma samples had much higher incidence of positive AKT and phosphorylated AKT (pAKT) protein staining than did benign ovarian cystadenoma samples (p < 0.01). The 5-year survival rate was only about 15% in patients with ovarian serous cystadenocarcinoma who had AKT and pAKT expression, whereas it was about 80% in those who did not have AKT or pAKT expression. Taken together, these results indicate that FSH increases the expression of VEGF by upregulating the expression of survivin, which is activated by the PI3K/AKT signaling pathway. Understanding the role of the PI3K/AKT pathway in FSH-stimulated expression of survivin and VEGF will be beneficial for evaluating the prognosis for patients with ovarian serous cystadenocarcinoma and for pursuing effective treatment against this disease.

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Section: Discussionmentioning

confidence: 99%

Section: Fsh Stimulation Of Survivin and Hif-1α Expression In Skov-3 mentioning

confidence: 95%

Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

et al. 2008

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“…S6K plays critical roles in the regulation of translation, cell growth, metastasis, and survival (10), and its overexpression has been linked to aggressive malignant phenotypes (9,(11)(12)(13). Because of its pivotal role in these processes, S6K has been recognized as a promising therapeutic target for a number of human cancers (10,12,14,15). Genetic and pharmacological suppression of the S6K pathway has been shown to prevent malignant transformation and block cancer progression (9,(15)(16)(17).…”

mentioning

confidence: 99%

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Byun

Lim

Mun

et al. 2015

Journal of Biological Chemistry

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Background: An underlying cause of cancer therapeutic resistance is the hyperactivation of endogenous overlapping or redundant signaling pathways in cancer cells. Results: Gingerenone A selectively kills cancer cells through dual inhibition of JAK2 and S6K1. Conclusion: Co-targeting JAK2 and S6K1 induces synergistic anti-cancer effects. Significance: Investigating the targets of bioactive compounds can lead to suggestions for novel therapeutic strategies.

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“…It could not be ruled out that ROS also affects other molecular pathways in addition to HIF-1α stabilization. p70S6K1 may be another molecule that is activated by ROS produced from treatment with EGF or insulin (Liu et al, 2006;Zhou et al, 2007). Paclitaxel-resistance was also induced by thymosin beta 4 (TB4) gene-overexpression (Oh et al, 2006) and TB4 proteins induced HIF-1α stabilization .…”

Section: Discussionmentioning

confidence: 99%

Hypoxia Induces Paclitaxel-Resistance through ROS Production

Oh¹,

Ryu²,

Lim³

et al. 2010

Biomolecules and Therapeutics

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-Oxygen supply into inside solid tumor is often diminished, which is called hypoxia. Many gene transcriptions were activated by hypoxia-inducible factor (HIF)-1α. Here, we investigated the effect of hypoxia on paclitaxel-resistance induction in HeLa cervical tumor cells. When HeLa cells were incubated under hypoxia condition, HIF-1α level was increased. In contrast, paclitaxel-mediated tumor cell death was reduced by the incubation under hypoxia condition. Paclitaxel-mediated tumor cell death was also inhibited by treatment with DMOG, chemical HIF-1α stabilizer, in a dose-dependent manner. A significant increase in intracellular ROS level was detected by the incubation under hypoxia condition. A basal level of cell density was increased in response to 10 nM H2O2. HIF-1α level was increased by treatment with various concentration of H 2 O 2 . The increased level of HIF-1α by hypoxia was reduced by the treatment with N-acetylcysteine (NAC), a well-known ROS scavenger. Paclitaxel-mediated tumor cell death was increased by treatment with NAC. Taken together, these findings demonstrate that hypoxia could play a role in paclitaxel-resistance induction through ROS-mediated HIF-1α stabilization. These results suggest that hypoxia-induced ROS could, in part, control tumor cell death through an increase in HIF-1α level.

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Reactive oxygen species regulate epidermal growth factor-induced vascular endothelial growth factor and hypoxia-inducible factor-1α expression through activation of AKT and P70S6K1 in human ovarian cancer cells

Cited by 198 publications

References 66 publications

Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

Activation of the PI3K/AKT pathway mediates FSH-stimulated VEGF expression in ovarian serous cystadenocarcinoma

Identification of a Dual Inhibitor of Janus Kinase 2 (JAK2) and p70 Ribosomal S6 Kinase1 (S6K1) Pathways

Hypoxia Induces Paclitaxel-Resistance through ROS Production

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