Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux
The metabolism and apoptosis of tumor cells are important factors that increase their sensitivity to chemotherapeutic drugs. p53 and cisplatin not only induce tumor cell apoptosis, but also regulate the tumor cell metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) can inhibit gl...
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MDPI AG
2022-12-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/23/24/16034 |
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| author | Jiaying Fu Sihang Yu Xiyao Zhao Chaoke Zhang Luyan Shen Yanan Liu Huimei Yu |
| author_facet | Jiaying Fu Sihang Yu Xiyao Zhao Chaoke Zhang Luyan Shen Yanan Liu Huimei Yu |
| author_sort | Jiaying Fu |
| collection | DOAJ |
| description | The metabolism and apoptosis of tumor cells are important factors that increase their sensitivity to chemotherapeutic drugs. p53 and cisplatin not only induce tumor cell apoptosis, but also regulate the tumor cell metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) can inhibit glycolysis and promote more glucose metabolism in the pentose phosphate pathway. We speculate that the regulation of the TIGAR by the combination therapy of p53 and cisplatin plays an important role in increasing the sensitivity of tumor cells to cisplatin. In this study, we found that the combined treatment of p53 and cisplatin was able to inhibit the mitochondrial function, promote mitochondrial pathway-induced apoptosis, and increase the sensitivity. Furthermore, the expression of the TIGAR was inhibited after a combined p53 and cisplatin treatment, the features of the TIGAR that regulate the pentose phosphate pathway were inhibited, the glucose flux shifted towards glycolysis, and the localization of the complex of the TIGAR and Hexokinase 2 (HK2) on the mitochondria was also reduced. Therefore, the combined treatment of p53 and cisplatin may modulate a glycolytic flux through the TIGAR, altering the cellular metabolic patterns while increasing apoptosis. Taken together, our findings reveal that the TIGAR may serve as a potential therapeutic target to increase the sensitivity of lung cancer A549 cells to cisplatin. |
| first_indexed | 2024-03-09T16:18:26Z |
| format | Article |
| id | doaj.art-0aa607005b664f48ab7e5fb5cc153606 |
| institution | Directory Open Access Journal |
| issn | 1661-6596 1422-0067 |
| language | English |
| last_indexed | 2024-03-09T16:18:26Z |
| publishDate | 2022-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | International Journal of Molecular Sciences |
| spelling | doaj.art-0aa607005b664f48ab7e5fb5cc1536062023-11-24T15:31:44ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672022-12-0123241603410.3390/ijms232416034Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic FluxJiaying Fu0Sihang Yu1Xiyao Zhao2Chaoke Zhang3Luyan Shen4Yanan Liu5Huimei Yu6Department of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaDepartment of Pathophysiology, College of Basic Medical Sciences, Jilin University, Changchun 130021, ChinaThe metabolism and apoptosis of tumor cells are important factors that increase their sensitivity to chemotherapeutic drugs. p53 and cisplatin not only induce tumor cell apoptosis, but also regulate the tumor cell metabolism. The TP53-induced glycolysis and apoptosis regulator (TIGAR) can inhibit glycolysis and promote more glucose metabolism in the pentose phosphate pathway. We speculate that the regulation of the TIGAR by the combination therapy of p53 and cisplatin plays an important role in increasing the sensitivity of tumor cells to cisplatin. In this study, we found that the combined treatment of p53 and cisplatin was able to inhibit the mitochondrial function, promote mitochondrial pathway-induced apoptosis, and increase the sensitivity. Furthermore, the expression of the TIGAR was inhibited after a combined p53 and cisplatin treatment, the features of the TIGAR that regulate the pentose phosphate pathway were inhibited, the glucose flux shifted towards glycolysis, and the localization of the complex of the TIGAR and Hexokinase 2 (HK2) on the mitochondria was also reduced. Therefore, the combined treatment of p53 and cisplatin may modulate a glycolytic flux through the TIGAR, altering the cellular metabolic patterns while increasing apoptosis. Taken together, our findings reveal that the TIGAR may serve as a potential therapeutic target to increase the sensitivity of lung cancer A549 cells to cisplatin.https://www.mdpi.com/1422-0067/23/24/16034TIGARp53cisplatinapoptosisA549 cells |
| spellingShingle | Jiaying Fu Sihang Yu Xiyao Zhao Chaoke Zhang Luyan Shen Yanan Liu Huimei Yu Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux International Journal of Molecular Sciences TIGAR p53 cisplatin apoptosis A549 cells |
| title | Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux |
| title_full | Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux |
| title_fullStr | Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux |
| title_full_unstemmed | Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux |
| title_short | Inhibition of TIGAR Increases Exogenous p53 and Cisplatin Combination Sensitivity in Lung Cancer Cells by Regulating Glycolytic Flux |
| title_sort | inhibition of tigar increases exogenous p53 and cisplatin combination sensitivity in lung cancer cells by regulating glycolytic flux |
| topic | TIGAR p53 cisplatin apoptosis A549 cells |
| url | https://www.mdpi.com/1422-0067/23/24/16034 |
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