Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival
Abstract Background Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor typ...
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BMC
2025-01-01
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| Online Access: | https://doi.org/10.1186/s40659-024-00581-3 |
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| author | Bárbara Mora-Lagos María Elena Reyes Lorena Lobos-Gonzalez Matías del Campo Kurt Buchegger Louise Zanella Ismael Riquelme Carmen Gloria Ili Priscilla Brebi |
| author_facet | Bárbara Mora-Lagos María Elena Reyes Lorena Lobos-Gonzalez Matías del Campo Kurt Buchegger Louise Zanella Ismael Riquelme Carmen Gloria Ili Priscilla Brebi |
| author_sort | Bárbara Mora-Lagos |
| collection | DOAJ |
| description | Abstract Background Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (3D tumor spheroids), and animal models. Results The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone. Conclusions This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC. |
| format | Article |
| id | doaj-art-e0885092e4554be18d92425584cd4932 |
| institution | Kabale University |
| issn | 0717-6287 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Biological Research |
| spelling | doaj-art-e0885092e4554be18d92425584cd49322025-01-19T12:11:03ZengBMCBiological Research0717-62872025-01-0158111310.1186/s40659-024-00581-3Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survivalBárbara Mora-Lagos0María Elena Reyes1Lorena Lobos-Gonzalez2Matías del Campo3Kurt Buchegger4Louise Zanella5Ismael Riquelme6Carmen Gloria Ili7Priscilla Brebi8Instituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de ChileInstituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de ChileCentro de Medicina Regenerativa, Facultad de Medicina-Clínica Alemana, Universidad del DesarrolloCentro de Medicina Regenerativa, Facultad de Medicina-Clínica Alemana, Universidad del DesarrolloDepartment of Basic Sciences, Faculty of Medicine, Universidad de La FronteraDoctorado en Ciencias Médicas, Universidad de La FronteraInstituto de Ciencias Biomédicas, Facultad de Ciencias de la Salud, Universidad Autónoma de ChileLaboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La FronteraLaboratory of Integrative Biology (LIBi), Centro de Excelencia en Medicina Traslacional (CEMT), Scientific and Technological Bioresource Nucleus (BIOREN), Universidad de La FronteraAbstract Background Gastric cancer (GC) is a significant cancer-related cause of death worldwide. GC’s most used chemotherapeutic regimen is based on platinum drugs such as cisplatin (CDDP). However, CDDP chemoresistance reduces the survival rate of advanced GC. The immune C-C chemokine receptor type 5 (CCR5) have been proposed as a pivotal factor in cancer progression since its blockade has been linked with antineoplastic effects on tumor cell proliferation; nevertheless, its role in the chemoresistance of GC has not been elucidated. This study aimed to determine the effects induced by the CCR5 using Maraviroc (MVC), a highly selective CCR5 antagonist, on CDDP-resistant AGS cells (AGS R-CDDP), tumoroids (3D tumor spheroids), and animal models. Results The combined CDDP and MVC treatment reduced cell viability and inhibited tumoroid formation in AGS R-CDDP cells. The effects of the MVC/CDDP combination on apoptosis and cell cycle progression were correlated with the increase in CDDP (dose-dependent). The mRNA levels of C-C Motif Chemokine Ligand 5 (CCL5), the main ligand for CCR5, decreased significantly in cells treated with the MVC/CDDP combination. MVC in the MVC/CDDP combination improved the survival rate and biochemical parameters of CDDP-treated mice by reducing the side effects of CDDP alone. Conclusions This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.https://doi.org/10.1186/s40659-024-00581-3Gastric cancer (GC)Cisplatin (CDDP)ChemoresistanceC-C chemokine receptor type 5 (CCR5)C-C motif chemokine ligand 5 (CCL5)Maraviroc (MVC) |
| spellingShingle | Bárbara Mora-Lagos María Elena Reyes Lorena Lobos-Gonzalez Matías del Campo Kurt Buchegger Louise Zanella Ismael Riquelme Carmen Gloria Ili Priscilla Brebi Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival Biological Research Gastric cancer (GC) Cisplatin (CDDP) Chemoresistance C-C chemokine receptor type 5 (CCR5) C-C motif chemokine ligand 5 (CCL5) Maraviroc (MVC) |
| title | Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| title_full | Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| title_fullStr | Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| title_full_unstemmed | Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| title_short | Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| title_sort | maraviroc cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival |
| topic | Gastric cancer (GC) Cisplatin (CDDP) Chemoresistance C-C chemokine receptor type 5 (CCR5) C-C motif chemokine ligand 5 (CCL5) Maraviroc (MVC) |
| url | https://doi.org/10.1186/s40659-024-00581-3 |
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