Up‐regulation of survivin by <scp>AKT</scp> and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer

Sun, Xiaochuan; Dong, Xuesong; Lin, Lele; Jiang, Xian; Wei, Zheng; Zhai, Bo; Sun, Bo; Zhang, Qiang; Wang, Xiaolong; Jiang, Hongchi; Krissansen, Geoffrey W.; Qiao, Haiquan; Sun, Xueying

doi:10.1111/febs.12577

Cited by 80 publications

(76 citation statements)

References 45 publications

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“…Therefore, a high level of CD44v6 expression may also contribute to the aggressive phenotype. In addition, the upregulation of Survivin by HIF-1α and PTEN contributed to cisplatin (CDDP) resistance, indicating that inhibition of these pathways may be a potential strategy for overcoming CDDP resistance in the treatment of gastric cancer [29].…”

Section: Discussionmentioning

confidence: 99%

Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis

Chen

Liu

et al. 2014

PLoS ONE

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PurposeThis study was to quantitatively summarize published data for evaluating the clinical and prognostic significance of four proteins involved in hypoxia-inducible factor-1 (HIF-1α) regulation of the metastasis cascade.MethodsSearches were performed using the MEDLINE, EMBASE, Cochrane Library, and Chinese Biomedicine databases without any language restrictions. Studies were pooled and either the summary risk ratio (RR) or odds ratio (OR) was calculated. Potential sources of heterogeneity were sought out via subgroup and sensitivity analyses, and publication bias was also performed.ResultsSeventeen studies evaluated HIF-1α, 20 studies evaluated phosphatase and tensin homolog (PTEN), 20 studies evaluated Survivin, and 16 studies evaluated CD44v6. Our results showed that increased HIF-1α expression was linked to a poor 5-year overall survival (RR = 1.508; 95% confidence interval (CI) 1.318–1.725; P<0.001). Decreased survival was heavily influenced by advanced tumor invasion (OR = 3.050; 95% CI 2.067–4.501; P<0.001), lymph node metastasis (1415 patients; OR = 3.486, 95% CI 2.737–4.440; P<0.001), distant metastasis (OR = 6.635; 95% CI 1.855–23.738; P = 0.004), vascular invasion (OR = 2.368; 95% CI 1.725–3.252; P<0.001), dedifferentiation (OR = 2.112; 95% CI 1.410–3.163; P<0.001), tumor size (OR = 1.921; 95% CI 1.395–2.647; P<0.001), and a higher TNM stage (OR = 2.762; 95% CI 1.941–3.942; P<0.001). Similarly, aberrant expression of PTEN, CD44v6, and Survivin were also observed in tumors that correlated with poor OS. The higher ORs of death at 5 years were 1.637 (95% CI = 1.452–1.845; P<0.001), 1.901 (95% CI = 1.432–2.525; P<0.001), and 1.627 (95% CI = 1.384–1.913; P<0.001), respectively, with an OR>2 for the main stratified meta-analyses of clinical factors.ConclusionsOur findings indicate that HIF-1α/PTEN/CD44v6/Survivin, as measured by immunohistochemistry, can be used to predict the prognosis and potential for invasion and metastasis in Asian patients with gastric cancer. The development of strategies against this subset of proteins could lead to new therapeutic approaches.

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Section: Discussionmentioning

confidence: 99%

Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis

Chen

Liu

et al. 2014

PLoS ONE

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“…Genistein exhibited a similar effect in the present study, in which HIF-1α-mediated survivin expression under hypoxic conditions and HIF-1α inhibition by genistein in HUVECs led to reduced rather than completely diminished survivin expression, even in the presence of 200 μM of genistein, implying that hypoxiainduced survivin expression can be initiated through other molecular pathways besides HIF-1α. To the best of our knowledge, this is the first study that shows survivin expression can be stimulated by hypoxia and CoCl2-induced HIF-1α accumulation in HUVECs in a time-dependent manner, although other studies have found hypoxia up-regulates survivin expression in cancer cell lines [45].…”

Section: Discussionmentioning

confidence: 76%

The Effect and Mechanism of Celecoxib in Hypoxia-Induced Survivin Up-Regulation in HUVECs

Liu

Zhao

Cai

2015

Cell Physiol Biochem

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Background/Aims: To investigate the roles of hypoxia-inducible factor 1α (HIF-1α), cyclooxygenase-2 (Cox-2) and its product, Prostaglandin E2 (PGE₂), in the mechanisms underlying hypoxia-induced survivin expression in human umbilical vein endothelial cells (HUVECs) and to examine the effect of celecoxib, a selective Cox-2 inhibitor, on survivin expression. Methods: HUVECs were exposed to a normal (95% O₂) or hypoxic (3% O₂) environment for 24 hrs. We observed the localized expression of survivin, Cox-2 and HIF-1α in HUVECs using immunocytochemistry and detected the inhibitory effects of celecoxib on the growth of HUVECs using an MTT assay. mRNA and protein levels of Cox-2, HIF-1α and survivin were determined by real-time PCR and Western blot analysis under hypoxic conditions for 0, 6, 12, or 24 hrs. The time course changes of HIF-1α and survivin protein expression induced by cobalt chloride (CoCl₂) were studied using Western blot analysis. We then treated HUVECs under hypoxia for 24 hrs with celecoxib (a Cox-2 selective inhibitor), genistein (a HIF-1α inhibitor) or exogenous PGE₂ to further investigate the changes in hypoxia-induced survivin expression. Results: Following 24 hrs of hypoxic treatment, cells exhibited strongly positive survivin, HIF-1α and Cox-2 cytoplasmic staining. Celecoxib (65 μM) effectively inhibited cell proliferation under hypoxic conditions. The protein and mRNA levels of Cox-2, HIF-1α and survivin were increased under hypoxia. The patterns of HIF-1α and survivin expression induced by CoCl₂ were similar to those induced by exposure to hypoxia. Genistein partially blocked survivin expression. Celecoxib reversed the hypoxia-induced survivin expression, whereas the addition of PGE₂ partially restored this effect. Conclusions: Hypoxia-induced survivin expression in HUVECs may be mediated by dual interdependent mechanisms directly involving HIF-1α and indirectly involving the Cox-2/PGE₂ pathways. Celecoxib may offset hypoxia-induced survivin expression.

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“…Unfortunately, despite a wide variety of approaches, human gastric cancer remains a major challenge with fewer effective targeted therapies than other cancers. Recently, it was reported that YM155 promotes cisplatin-induced apoptosis in gastric cancer (22). Our research focused on the inhibitory effect of YM155 alone on gastric cancer.…”

Section: Discussionmentioning

confidence: 99%

Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) Stability Contributes to YM155 Resistance in Human Gastric Cancer Cells

Park¹,

Hong²,

Moon³

et al. 2015

Journal of Biological Chemistry

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Background: YM155, a survivin suppressant, has been shown anticancer efficacy in various cancer cells. Results: Human gastric cancer cells differentially displayed the sensitivity to YM155 dependent to degradation of cIAP1. Conclusion: Cellular inhibitor of apoptosis protein 1 (cIAP1) interacts with survivin to control their mutual stability and determine sensitivity to YM155. Significance: The regulation of cIAP1 enhances the efficacy for YM155 treatment in gastric cancer.

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Up‐regulation of survivin by AKT and hypoxia‐inducible factor 1α contributes to cisplatin resistance in gastric cancer

Cited by 80 publications

References 45 publications

Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis

Clinical and Prognostic Significance of HIF-1α, PTEN, CD44v6, and Survivin for Gastric Cancer: A Meta-Analysis

The Effect and Mechanism of Celecoxib in Hypoxia-Induced Survivin Up-Regulation in HUVECs

Cellular Inhibitor of Apoptosis Protein 1 (cIAP1) Stability Contributes to YM155 Resistance in Human Gastric Cancer Cells

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