Background: For the past few years, gene-therapy has recently shown considerable clinical benefit in cancer therapy, and the applications of gene therapies in cancer treatments continue to increase perennially. EZH2, an ideal candidate for tumor gene therapy, plays an important role in the tumorigenesis.
Methods: In this study, we developed a novel gene delivery system with a self-assembly method by Methoxy polyethylene glycol-polycaprolactone (MPEG-PCL) and DOTAP(DMC). And EZH2si-DMC was used to research anti-glioma both in vitro and in vivo.
Results: DMC with zeta-potential value of 36.7 mV and size of 35.6 nm showed good performance in the delivery siRNA to glioma cell in vitro with high 98% transfection efficiency. EZH2si-DMC showed good anti-glioma effect in vitro through inducing cell apoptosis and inhibiting cell growth. What's more, treatment of tumor-bearing mice with DMC-EZH2si complex had significantly inhibited tumor growth at the subcutaneous model in vivo by inhibiting EZH2 protein expression, promoting apoptosis and reducing proliferation.
Conclusion: The EZH2 siRNA and DMC complex may be used to treat the glioma in clinical as a new drug.
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http://dx.doi.org/10.2147/IJN.S189871 | DOI Listing |
Pharmaceuticals (Basel)
December 2024
Department of Neurosurgery, Brain Tumor Center, Erasmus MC Cancer Institute, Erasmus University Medical Center, 3015 GD Rotterdam, The Netherlands.
Background: Glioblastoma is an aggressive and incurable type of brain cancer. Little progress has been made in the development of effective new therapies in the past decades. The blood-brain barrier (BBB) and drug efflux pumps, which together hamper drug delivery to these tumors, play a pivotal role in the gap between promising preclinical findings and failure in clinical trials.
View Article and Find Full Text PDFNaunyn Schmiedebergs Arch Pharmacol
December 2024
Department of Neurosurgery, the Second Affiliated Hospital of Nanchang University, No. 1 Minde Road, Donghu District, Nanchang City, Jiangxi, 330006, China.
In clinical settings, glioma patients often develop secondary resistance to first-line chemotherapy drugs. Vincristine has been reported for its application in cancer chemotherapy, but its molecular mechanism of action remains unclear. This study aimed to identify potential targets of vincristine in glioma using network pharmacology and to experimentally validate the possible molecular mechanisms against glioma.
View Article and Find Full Text PDFCell Death Dis
November 2024
Department of Neurosurgery, the Second Hospital & Clinical Medical School, Lanzhou University, Lanzhou, China.
Glioma is a common primary nervous system malignant tumor with poor overall cure rate and low survival rate, yet successful treatment still remains a challenge. Here, we demonstrated that amantadine (AMT) exhibits the powerful anti-glioma effect by promoting apoptosis and autophagy in vivo and in vitro. Mechanistically, amantadine induces a large amount of reactive oxygen species (ROS) accumulation in glioma cells, and then triggers apoptosis by destroying mitochondria.
View Article and Find Full Text PDFAdv Sci (Weinh)
December 2024
Department of Neurosurgery and Institute of Neurosurgery, State Key Laboratory of Biotherapy and Cancer Center, West China Hospital, West China Medical School, Sichuan University and Collaborative Innovation Center for Biotherapy, Chengdu, 610041, China.
Temozolomide (TMZ) serves as the principal chemotherapeutic agent for glioma; nonetheless, its therapeutic efficacy is compromised by the rapid emergence of drug resistance, the inadequate targeting of glioma cells, and significant systemic toxicity. ARV-825 may play a role in modulating drug resistance by degrading the BRD4 protein, thereby exerting anti-glioma effects. Therefore, to surmount TMZ resistance and achieve efficient and specific drug delivery, a dual-targeted glutathione (GSH)-responsive nanoparticle system (T+A@Glu-NP) is designed and synthesized for the co-delivery of ARV-825 and TMZ.
View Article and Find Full Text PDFChem Biodivers
November 2024
School of Pharmacy, Guizhou University of Traditional Chinese Medicine, Guiyang, 550025, People's Republic of China.
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