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Combination treatment with VPA and MSCs‑TRAIL could increase anti‑tumor effects against intracranial glioma
Soon A Park1, Hye Rim Han1, Stephen Ahn2
1Department of Biomedicine and Health Sciences, College of Medicine, The Catholic University of Korea, Seoul 06591, Republic of Korea.
Abstract:
Human bone marrow‑derived mesenchymal stem cells secreting tumor necrosis factor‑related apoptosis‑inducing ligand (MSCs‑TRAIL) have demonstrated effective anti‑tumor activity against various tumors including lung, pancreatic and prostate tumors, although several tumor types are not responsive. In such case, other reagents may decrease tumor growth via TRAIL‑mediated cell death. The present study aimed to examine the effectiveness of valproic acid (VPA) in enhancing the efficacy of TRAIL, which was delivered using MSCs. Moreover, the present study examined the induced tumor tropism of MSCs via cell viability and migration assays. Combination treatment with VPA and MSCs‑TRAIL enhanced the glioma therapeutic effect by increasing death receptor 5 and caspase activation. Migration assays identified increased MSC migration in VPA and MSCs‑TRAIL‑treated glioma cells and in the tumor site in glioma‑bearing mice compared with VPA or MSC‑TRAIL treatment alone. In vivo experiments demonstrated that MSC‑based TRAIL gene delivery to VPA‑treated tumors had greater therapeutic efficacy compared with treatment with each agent alone. These findings suggested that VPA treatment increased the therapeutic efficacy of MSC‑TRAIL via TRAIL‑induced apoptosis and enhanced tropism of MSCs, which may offer a useful strategy for tumor gene therapy.
Insights
Valproic acid (VPA) enhances mesenchymal stem cells secreting tumor necrosis factor-related apoptosis-inducing ligand (MSCs-TRAIL) therapy for glioma. Combination treatment boosts anti-tumor effects and stem cell migration, improving overall therapeutic efficacy in vivo.
Area of Science:
- Oncology
- Stem Cell Therapy
- Molecular Biology
Background:
- Mesenchymal stem cells secreting tumor necrosis factor-related apoptosis-inducing ligand (MSCs-TRAIL) show anti-tumor potential but face limitations with unresponsive tumors.
- TRAIL-mediated apoptosis is a key mechanism for tumor cell death, and enhancing this pathway is crucial for effective cancer therapy.
Purpose of the Study:
- To investigate the synergistic effect of valproic acid (VPA) with MSCs-TRAIL in enhancing glioma treatment.
- To evaluate the impact of VPA on the tumor tropism and migration of MSCs in the context of glioma therapy.
Main Methods:
- Combination therapy using VPA and MSCs-TRAIL was administered to glioma models.
- Cell viability, migration assays, and in vivo experiments were conducted to assess therapeutic efficacy.
- Analysis included examining death receptor 5 and caspase activation in tumor cells.
Main Results:
- Combination treatment significantly enhanced the therapeutic effect against glioma by increasing death receptor 5 and caspase activation.
- VPA treatment led to increased migration of MSCs towards glioma cells and within the tumor site in vivo.
- In vivo experiments showed superior therapeutic efficacy of MSC-based TRAIL gene delivery in VPA-pretreated tumors compared to monotherapy.
Conclusions:
- VPA significantly potentiates the anti-glioma efficacy of MSCs-TRAIL by augmenting TRAIL-induced apoptosis and improving MSC tumor tropism.
- This combination strategy holds promise as a novel approach for effective tumor gene therapy, particularly for challenging cancers.
