期刊
MOLECULAR THERAPY-ONCOLYTICS
卷 24, 期 -, 页码 707-718出版社
CELL PRESS
DOI: 10.1016/j.omto.2022.01.013
关键词
-
资金
- National Natural Science Foundation of China [81702482]
- Precision Medicine Research Fund of Taihe Hospital [2016JZ01]
This study investigated the effectiveness of an mRNA-based therapeutic strategy using PTEN-mRNA and TRAIL-mRNA in tumor cells derived from PTEN-deletion patients. The combination treatment of PTEN-mRNA and TRAIL-mRNA showed significant tumor growth suppression and the JNK pathway may be involved. This study provides a basis for developing an mRNA-based therapeutic strategy for GBM.
Glioblastoma (GBM) is characterized as having high molecular heterogeneity and complexity, which can be well revealed by genomic study. A truly effective treatment for GBM should flexibly address its heterogeneities, complexity, and strong drug resistance. This study was performed to explore the effectiveness of an mRNA-based therapeutic strategy using in vitro synthesized PTEN-mRNA and TRAIL-mRNA in tumor cells derived from PTEN-deletion patients. The PTEN gene alterations were revealed by whole-exome sequencing of three paired clinical GBMs and selected as the therapy target. Patient-derived primary glioblastoma stem cells (GBM2) and a DBTRG-cell-derived xenograft were used to detect mRNA's cytotoxicity in vitro and tumor suppression in vivo. Following the successful in vitro synthesis of PTEN-mRNA and TRAIL-mRNA, the combinational treatment of PTEN-mRNA and TRAIL-mRNA significantly suppressed tumor growth compared with treatment with PBS (96.4%), PTEN-mRNA (89.7%), and TRAIL-mRNA (84.5%). The combinational application of PTEN-mRNA and TRAIL-mRNA showed synergistic inhibition of tumor growth, and the JNK pathway might be the major mechanism involved. This study provided a basis for an mRNA-based therapeutic strategy to be developed into an effective patient-tailored treatment for GBM.
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