Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma
Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl i...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-09-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/14/19/4553 |
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| author | Sonia Simón Serrano Michele Tavecchio Josef Mallik Alvar Grönberg Eskil Elmér Chamseddine Kifagi Philippe Gallay Magnus Joakim Hansson Ramin Massoumi |
| author_facet | Sonia Simón Serrano Michele Tavecchio Josef Mallik Alvar Grönberg Eskil Elmér Chamseddine Kifagi Philippe Gallay Magnus Joakim Hansson Ramin Massoumi |
| author_sort | Sonia Simón Serrano |
| collection | DOAJ |
| description | Hepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl isomerase activity—have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment. |
| first_indexed | 2024-03-09T21:59:57Z |
| format | Article |
| id | doaj.art-ceb348f036d245488dbec12259e07c51 |
| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-03-09T21:59:57Z |
| publishDate | 2022-09-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-ceb348f036d245488dbec12259e07c512023-11-23T19:52:39ZengMDPI AGCancers2072-66942022-09-011419455310.3390/cancers14194553Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular CarcinomaSonia Simón Serrano0Michele Tavecchio1Josef Mallik2Alvar Grönberg3Eskil Elmér4Chamseddine Kifagi5Philippe Gallay6Magnus Joakim Hansson7Ramin Massoumi8Translational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, SE-223 63 Lund, SwedenAbliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, SwedenTranslational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, SE-223 63 Lund, SwedenAbliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, SwedenAbliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, SwedenNGS & OMICS Data Analysis (NODA) Consulting, Flöjtvägen 10b, SE-224 68 Lund, SwedenDepartment of Immunology & Microbial Science, The Scripps Research Institute, La Jolla, CA 92037, USAAbliva AB, Medicon Village, Scheelevägen 2, SE-233 81 Lund, SwedenTranslational Cancer Research, Department of Laboratory Medicine, Lund University, Medicon Village, SE-223 63 Lund, SwedenHepatocellular carcinoma (HCC), commonly diagnosed at an advanced stage, is the most common primary liver cancer. Owing to a lack of effective HCC treatments and the commonly acquired chemoresistance, novel therapies need to be investigated. Cyclophilins—intracellular proteins with peptidyl-prolyl isomerase activity—have been shown to play a key role in therapy resistance and cell proliferation. Here, we aimed to evaluate changes in the gene expression of HCC cells caused by cyclophilin inhibition in order to explore suitable combination treatment approaches, including the use of chemoagents, such as cisplatin. Our results show that the novel cyclophilin inhibitor NV651 decreases the expression of genes involved in several pathways related to the cancer cell cycle and DNA repair. We evaluated the potential synergistic effect of NV651 in combination with other treatments used against HCC in cisplatin-sensitive cells. NV651 showed a synergistic effect in inhibiting cell proliferation, with a significant increase in intrinsic apoptosis in combination with the DNA crosslinking agent cisplatin. This combination also affected cell cycle progression and reduced the capacity of the cell to repair DNA in comparison with a single treatment with cisplatin. Based on these results, we believe that the combination of cisplatin and NV651 may provide a novel approach to HCC treatment.https://www.mdpi.com/2072-6694/14/19/4553synergycyclophilinPPIaseapoptosishepatocellular carcinomacisplatin |
| spellingShingle | Sonia Simón Serrano Michele Tavecchio Josef Mallik Alvar Grönberg Eskil Elmér Chamseddine Kifagi Philippe Gallay Magnus Joakim Hansson Ramin Massoumi Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma Cancers synergy cyclophilin PPIase apoptosis hepatocellular carcinoma cisplatin |
| title | Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma |
| title_full | Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma |
| title_fullStr | Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma |
| title_full_unstemmed | Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma |
| title_short | Synergistic Effects of Sanglifehrin-Based Cyclophilin Inhibitor NV651 with Cisplatin in Hepatocellular Carcinoma |
| title_sort | synergistic effects of sanglifehrin based cyclophilin inhibitor nv651 with cisplatin in hepatocellular carcinoma |
| topic | synergy cyclophilin PPIase apoptosis hepatocellular carcinoma cisplatin |
| url | https://www.mdpi.com/2072-6694/14/19/4553 |
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