Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells
The aim of this study was to increase somatostatin type-2 receptor (SSTR2) expression on neuroendocrine tumor (NET) cells using histone deacetylase inhibitors (HDACis), potentially increasing the uptake of SSTR2-targeted radiopharmaceuticals and subsequently improving treatment efficacy of peptide r...
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MDPI AG
2021-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/13/19/4905 |
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| author | Maria J. Klomp Simone U. Dalm Peter M. van Koetsveld Fadime Dogan Marion de Jong Leo J. Hofland |
| author_facet | Maria J. Klomp Simone U. Dalm Peter M. van Koetsveld Fadime Dogan Marion de Jong Leo J. Hofland |
| author_sort | Maria J. Klomp |
| collection | DOAJ |
| description | The aim of this study was to increase somatostatin type-2 receptor (SSTR2) expression on neuroendocrine tumor (NET) cells using histone deacetylase inhibitors (HDACis), potentially increasing the uptake of SSTR2-targeted radiopharmaceuticals and subsequently improving treatment efficacy of peptide receptor radionuclide therapy (PRRT). Human NET cell lines BON-1, NCI-H727, and GOT1 were treated with HDACis (i.e., CI-994, entinostat, LMK-235, mocetinostat, panobinostat, or valproic acid (VPA); entinostat and VPA were the HDACis tested in GOT1 cells) to examine <i>SSTR2</i> mRNA expression levels and uptake of SSTR2-targeting radiotracer [<sup>111</sup>In]In-DOTATATE. Reversibility of the induced effects was examined after drug-withdrawal. Finally, the effect of VPA on radiosensitivity was investigated. A strong stimulatory effect in BON-1, NCI-H727, and GOT1 cells was observed after HDACi treatment, both on <i>SSTR2</i> mRNA expression levels and [<sup>111</sup>In]In-DOTATATE uptake. The effects of the HDACis were largely reversible over a period of seven days, demonstrating largest reductions within the first day. The reversibility profile of the induced effects suggests that proper timing of HDACi treatment is most likely essential for a beneficial outcome. In addition to increasing SSTR2 expression levels, VPA enhanced the radiosensitivity of all cell lines. In conclusion, HDACi treatment increased SSTR2 expression, and radiosensitivity was also enhanced upon VPA treatment. |
| first_indexed | 2024-03-10T07:04:32Z |
| format | Article |
| id | doaj.art-269e5ef6f1df4186a9dafa553e4092e4 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-10T07:04:32Z |
| publishDate | 2021-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-269e5ef6f1df4186a9dafa553e4092e42023-11-22T15:54:06ZengMDPI AGCancers2072-66942021-09-011319490510.3390/cancers13194905Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET CellsMaria J. Klomp0Simone U. Dalm1Peter M. van Koetsveld2Fadime Dogan3Marion de Jong4Leo J. Hofland5Department of Radiology and Nuclear Medicine, Erasmus MC, 3015 GD Rotterdam, The NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC, 3015 GD Rotterdam, The NetherlandsDepartment of Internal Medicine, Division of Endocrinology, Erasmus MC, 3015 GD Rotterdam, The NetherlandsDepartment of Internal Medicine, Division of Endocrinology, Erasmus MC, 3015 GD Rotterdam, The NetherlandsDepartment of Radiology and Nuclear Medicine, Erasmus MC, 3015 GD Rotterdam, The NetherlandsDepartment of Internal Medicine, Division of Endocrinology, Erasmus MC, 3015 GD Rotterdam, The NetherlandsThe aim of this study was to increase somatostatin type-2 receptor (SSTR2) expression on neuroendocrine tumor (NET) cells using histone deacetylase inhibitors (HDACis), potentially increasing the uptake of SSTR2-targeted radiopharmaceuticals and subsequently improving treatment efficacy of peptide receptor radionuclide therapy (PRRT). Human NET cell lines BON-1, NCI-H727, and GOT1 were treated with HDACis (i.e., CI-994, entinostat, LMK-235, mocetinostat, panobinostat, or valproic acid (VPA); entinostat and VPA were the HDACis tested in GOT1 cells) to examine <i>SSTR2</i> mRNA expression levels and uptake of SSTR2-targeting radiotracer [<sup>111</sup>In]In-DOTATATE. Reversibility of the induced effects was examined after drug-withdrawal. Finally, the effect of VPA on radiosensitivity was investigated. A strong stimulatory effect in BON-1, NCI-H727, and GOT1 cells was observed after HDACi treatment, both on <i>SSTR2</i> mRNA expression levels and [<sup>111</sup>In]In-DOTATATE uptake. The effects of the HDACis were largely reversible over a period of seven days, demonstrating largest reductions within the first day. The reversibility profile of the induced effects suggests that proper timing of HDACi treatment is most likely essential for a beneficial outcome. In addition to increasing SSTR2 expression levels, VPA enhanced the radiosensitivity of all cell lines. In conclusion, HDACi treatment increased SSTR2 expression, and radiosensitivity was also enhanced upon VPA treatment.https://www.mdpi.com/2072-6694/13/19/4905neuroendocrine tumorspeptide receptor radionuclide therapysomatostatin type-2 receptorsSSTR2[<sup>111</sup>In]In-DOTATATEupregulation |
| spellingShingle | Maria J. Klomp Simone U. Dalm Peter M. van Koetsveld Fadime Dogan Marion de Jong Leo J. Hofland Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells Cancers neuroendocrine tumors peptide receptor radionuclide therapy somatostatin type-2 receptors SSTR2 [<sup>111</sup>In]In-DOTATATE upregulation |
| title | Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells |
| title_full | Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells |
| title_fullStr | Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells |
| title_full_unstemmed | Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells |
| title_short | Comparing the Effect of Multiple Histone Deacetylase Inhibitors on SSTR2 Expression and [<sup>111</sup>In]In-DOTATATE Uptake in NET Cells |
| title_sort | comparing the effect of multiple histone deacetylase inhibitors on sstr2 expression and sup 111 sup in in dotatate uptake in net cells |
| topic | neuroendocrine tumors peptide receptor radionuclide therapy somatostatin type-2 receptors SSTR2 [<sup>111</sup>In]In-DOTATATE upregulation |
| url | https://www.mdpi.com/2072-6694/13/19/4905 |
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