Maraviroc/cisplatin combination inhibits gastric cancer tumoroid growth and improves mice survival

Abstract

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.

Keywords

• Gastric cancer (GC)
• Cisplatin (CDDP)
• Chemoresistance
• C-C chemokine receptor type 5 (CCR5)
• C-C motif chemokine ligand 5 (CCL5)
• Maraviroc (MVC)