Detailed Abstract
[Poster Presentation 12 - Biliary & Pancreas (Pancreas Disease/Surgery)]
[PP 12-3] THE EFFECT OF MCT4 INHIBITION ON THE ANTICANCER ACTIVITY OF IRINOTECAN: AN EVALUATION OF ITS THERAPEUTIC POTENTIAL IN PANCREATIC DUCTAL ADENOCARCINOMA (PDAC)
Moon-Gyu CHO 1, Seung Yoon RHO 2, Myung Sup KIM 1, Kyung-Hee CHUN 3, Chang Moo KANG 4
1 Biochemistry And Molecular Biology, Yonsei University College of Medicine, Korea, 2 Surgery, Yongin Severance Hospital, Yonsei University, Korea, 3 Institute for Bio-medical Convergence Science And Technology, Yonsei University, Korea, 4 Pancreatobiliary Cancer Center, Cancer Hospital, Yonsei University, Korea
Background : Pancreatic ductal adenocarcinoma (PDAC) is among the most aggressive cancers, characterized by poor prognosis and limited treatment options. Irinotecan, a topoisomerase I inhibitor, has shown potential in treating PDAC but is hindered by significant side effects and limited efficacy. Monocarboxylate transporter 4 (MCT4) overexpression in PDAC contributes to metabolic reprogramming and chemoresistance, making it a promising therapeutic target.
Methods : Human PDAC cell lines were cultured in standard medium and treated with irinotecan, VB124 (MCT4 inhibitor), or their combination. The combination treatment involved reducing irinotecan concentration by 50%. Cell viability was assessed using a Ez-cytox assay kit after 96 hours. Western blotting was performed to evaluate MCT4 expression. Statistical analysis was conducted using one-way ANOVA with Tukey’s post hoc test. cells were transfected with MCT4-targeting siRNA using Lipofectamine™ RNAiMAX. For colony formation, treated cells were seeded at low density and incubated for 10–14 days.
Results : Inhibition of MCT4 led to a reduction in colony formation and migration ability. Combination therapy with irinotecan and VB124 demonstrated comparable cell death effects to irinotecan monotherapy, even with a 50% reduced irinotecan dose. This indicates that the dual therapy approach maintains efficacy while potentially minimizing irinotecan-related side effects.
Conclusions : Targeting MCT4 overexpression with a combination of irinotecan and an MCT4 inhibitor presents a promising strategy for enhancing PDAC treatment efficacy. This approach may reduce toxicity and improve patient outcomes, offering a novel therapeutic avenue for this challenging malignancy.
Methods : Human PDAC cell lines were cultured in standard medium and treated with irinotecan, VB124 (MCT4 inhibitor), or their combination. The combination treatment involved reducing irinotecan concentration by 50%. Cell viability was assessed using a Ez-cytox assay kit after 96 hours. Western blotting was performed to evaluate MCT4 expression. Statistical analysis was conducted using one-way ANOVA with Tukey’s post hoc test. cells were transfected with MCT4-targeting siRNA using Lipofectamine™ RNAiMAX. For colony formation, treated cells were seeded at low density and incubated for 10–14 days.
Results : Inhibition of MCT4 led to a reduction in colony formation and migration ability. Combination therapy with irinotecan and VB124 demonstrated comparable cell death effects to irinotecan monotherapy, even with a 50% reduced irinotecan dose. This indicates that the dual therapy approach maintains efficacy while potentially minimizing irinotecan-related side effects.
Conclusions : Targeting MCT4 overexpression with a combination of irinotecan and an MCT4 inhibitor presents a promising strategy for enhancing PDAC treatment efficacy. This approach may reduce toxicity and improve patient outcomes, offering a novel therapeutic avenue for this challenging malignancy.
SESSION
Poster Presentation 12
Exhibition Hall 3/28/2025 2:20 PM - 3:00 PM