Title : Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism.

Pub. Date : 2016 Apr 1

PMID : 26801746






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1 Overcoming cisplatin resistance of ovarian cancer cells by targeting HIF-1-regulated cancer metabolism. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
2 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
3 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
4 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
5 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
6 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
7 By using two pairs of genetically matched cisplatin-sensitive and cisplatin-resistant ovarian cancer cell lines, we tested the hypothesis that downregulating hypoxia-inducible factor-1 (HIF-1), which regulates metabolic enzymes involved in glycolysis, is a promising strategy for overcoming cisplatin resistance of human ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
8 We found that cisplatin downregulated the level of the regulatable alpha subunit of HIF-1, HIF-1alpha, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1alpha degradation but did not downregulate HIF-1alpha in their cisplatin-resistant counterparts. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
9 We found that cisplatin downregulated the level of the regulatable alpha subunit of HIF-1, HIF-1alpha, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1alpha degradation but did not downregulate HIF-1alpha in their cisplatin-resistant counterparts. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
10 We found that cisplatin downregulated the level of the regulatable alpha subunit of HIF-1, HIF-1alpha, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1alpha degradation but did not downregulate HIF-1alpha in their cisplatin-resistant counterparts. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
11 We found that cisplatin downregulated the level of the regulatable alpha subunit of HIF-1, HIF-1alpha, in cisplatin-sensitive ovarian cancer cells through enhancing HIF-1alpha degradation but did not downregulate HIF-1alpha in their cisplatin-resistant counterparts. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
12 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
13 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
14 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
15 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
16 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
17 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
18 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
19 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
20 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
21 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
22 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
23 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
24 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
25 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
26 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
27 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
28 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
29 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
30 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
31 Overexpression of a degradation-resistant HIF-1alpha (HIF-1alpha DeltaODD) reduced cisplatin-induced apoptosis in cisplatin-sensitive cells, whereas genetic knockdown of HIF-1alpha or pharmacological promotion of HIF-1alpha degradation enhanced response to cisplatin in both cisplatin-sensitive and cisplatin-resistant ovarian cancer cells. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
32 We further demonstrated that knockdown of HIF-1alpha improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
33 We further demonstrated that knockdown of HIF-1alpha improved the response of cisplatin-resistant ovarian cancer cells to cisplatin by redirecting the aerobic glycolysis in the resistant cancer cells toward mitochondrial oxidative phosphorylation, leading to cell death through overproduction of reactive oxygen species. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens
34 Our findings suggest that the HIF-1alpha-regulated cancer metabolism pathway could be a novel target for overcoming cisplatin resistance in ovarian cancer. Cisplatin hypoxia inducible factor 1 subunit alpha Homo sapiens