Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival
Journal
Biological Research
ISSN
0717-6287
Date Issued
2025-01-18
Author(s)
Bárbara Mora-Lagos
María Elena Reyes
Matías del Campo
Kurt Buchegger
Louise Zanella
Ismael Riquelme
Carmen Gloria Ili
Priscilla Brebi
Type
journal-article
Abstract
<jats:title>Abstract</jats:title>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>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 (<jats:italic>3D</jats:italic> tumor spheroids), and animal models.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Background</jats:title>
<jats:p>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 (<jats:italic>3D</jats:italic> tumor spheroids), and animal models.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Results</jats:title>
<jats:p>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.</jats:p>
</jats:sec>
<jats:sec>
<jats:title>Conclusions</jats:title>
<jats:p>This finding suggests that MVC/CDDP combination could be a potential complementary therapy for GC.</jats:p>
</jats:sec>
Subjects
animals
;
antineoplastic agents
;
antineoplastic combined chemotherapy protocols
;
apoptosis
;
ccr5 receptor antagonists
;
cell line, tumor
;
cell proliferation
;
cell survival
;
cisplatin
;
cyclohexanes
;
drug resistance, neoplasm
;
humans
;
male
;
maraviroc
;
mice
;
mice, inbred balb c
;
mice, nude
;
stomach neoplasms
;
triazoles
;
antineoplastic agent
;
chemokine receptor ccr5 antagonist
;
cisplatin
;
cyclohexane derivative
;
maraviroc
;
triazole derivative
;
animal
;
apoptosis
;
bagg albino mouse
;
cell proliferation
;
cell survival
;
drug effect
;
drug resistance
;
drug therapy
;
human
;
male
;
mouse
;
nude mouse
;
stomach tumor
;
tumor cell line