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Combination treatment with VPA and MSCs‑TRAIL could increase anti‑tumor effects against intracranial glioma.

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.

SUBMITTER: Park SA

PROVIDER: S-EPMC7859926 | biostudies-literature | 2021 Mar

REPOSITORIES: biostudies-literature

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Combination treatment with VPA and MSCs‑TRAIL could increase anti‑tumor effects against intracranial glioma.

Park Soon A SA Han Hye Rim HR Ahn Stephen S Ryu Chung Heon CH Jeun Sin-Soo SS

Oncology reports 20210114 3

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 ...[more]

PMID: 33469674

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Project description:Rationale: Osteosarcoma (OS), a common malignant bone tumor, calls for the investigation of novel treatment strategies. Low-intensity vibration (LIV) presents itself as a promising option, given its potential to enhance bone health and decrease cancer susceptibility. This research delves into the effects of LIV on OS cells and mesenchymal stem cells (MSCs), with a primary focus on generating induced tumor-suppressing cells (iTSCs) and tumor-suppressive conditioned medium (CM). Methods: To ascertain the influence of vibration frequency, we employed numerical simulations and conducted experiments to determine the most effective LIV conditions. Subsequently, we generated iTSCs and CM through LIV exposure and assessed the impact of CM on OS cells. We also explored the underlying mechanisms of the tumor-suppressive effects of LIV-treated MSC CM, with a specific focus on vinculin (VCL). We employed cytokine array, RNA sequencing, and Western blot techniques to investigate alterations in cytokine profiles, transcriptomes, and tumor suppressor proteins. Results: Numerical simulations validated LIV frequencies within the 10-100 Hz range. LIV induced notable morphological changes in OS cells and MSCs, confirming its dual role in inhibiting OS cell progression and promoting MSC conversion into iTSCs. Upregulated VCL expression enhanced MSC responsiveness to LIV, significantly bolstering CM's efficacy. Notably, we identified tumor suppressor proteins in LIV-treated CM, including procollagen C endopeptidase enhancer (PCOLCE), histone H4 (H4), peptidylprolyl isomerase B (PPIB), and aldolase A (ALDOA). Consistently, cytokine levels decreased significantly in LIV-treated mouse femurs, and oncogenic transcript levels were downregulated in LIV-treated OS cells. Moreover, our study demonstrated that combining LIV-treated MSC CM with chemotherapy drugs yielded additive anti-tumor effects. Conclusions: LIV effectively impeded the progression of OS cells and facilitated the transformation of MSCs into iTSCs. Notably, iTSC-derived CM demonstrated robust anti-tumor properties and the augmentation of MSC responsiveness to LIV via VCL. Furthermore, the enrichment of tumor suppressor proteins within LIV-treated MSC CM and the reduction of cytokines within LIV-treated isolated bone underscore the pivotal tumor-suppressive role of LIV within the bone tumor microenvironment.

Dataset Information

Combination treatment with VPA and MSCs‑TRAIL could increase anti‑tumor effects against intracranial glioma.

Publications

Combination treatment with VPA and MSCs‑TRAIL could increase anti‑tumor effects against intracranial glioma.

Similar Datasets

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