title: Lumbar puncture-administered resveratrol inhibits STAT3 activation, enhancing autophagy and apoptosis in orthotopic rat glioblastomas.
abstract: Trans-resveratrol suppresses glioblastoma growth in vitro, but its effects on intracranial glioblastomas remain untested. Resveratrol crosses the blood-brain barrier, and lumbar puncture (LP) greatly increases its bioavailability in rat brains; therefore, we investigated the effectiveness of LP-administered resveratrol on orthotopic rat glioblastomas. Twenty-four tumor-bearing rats were separated into two groups: Group 1 receiving 100 μl saline containing 0.3% DMSO and Group 2 receiving 100 μl resveratrol (300 μM). Treatments started 3 days after transplantation in 2-day intervals until death. Intracranial drug availabilities, tumor sizes, average life spans and the impacts on STAT3 signaling, apoptosis and autophagy rates were evaluated. MRI imaging revealed that average tumor size in the LP group (495.8 ± 22.3 mm2) was smaller than the control groups (810.3 ± 56.4 mm2; P<0.05). The mean survival time in the LP group (22.2 ± 2.1 d) was longer than control animals (16.0 ± 1.8 d; P<0.05). LP resveratrol-treated glioblastomas showed less Cyclin D1 staining, enhanced autophagy with up-regulated LC3 and Beclin1 expression, and widely distributed apoptotic foci around tumor capillaries with suppressed STAT3 expression and nuclear translocation. In conclusion, LP-delivered resveratrol efficiently inhibited orthotopic rat glioblastoma growth by inactivating STAT3 signaling and enhancing autophagy and apoptosis.
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Song
authors.initials: S
authors.lastname: Xue
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Shu
authors.initials: S
authors.lastname: Xiao-Hong
authors.affiliation: Department of Radiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Sha
authors.initials: S
authors.lastname: Lin
authors.affiliation: Department of Radiology, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Bian
authors.initials: B
authors.lastname: Jie
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Li-Li
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Gu
authors.initials: G
authors.lastname: Jia-Yao
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Shi
authors.initials: S
authors.lastname: Shun
authors.affiliation: Department of Orthopedics, Second Affiliated Hospital of Dalian Medical University, Dalian 116023, China.
authors.forename: Li
authors.initials: L
authors.lastname: Pei-Nan
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Wu
authors.initials: W
authors.lastname: Mo-Li
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Wang
authors.initials: W
authors.lastname: Qian
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Xiao-Yan
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Kong
authors.initials: K
authors.lastname: Qing-You
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Zhang
authors.initials: Z
authors.lastname: Peng
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Li
authors.initials: L
authors.lastname: Hong
authors.affiliation: Liaoning Laboratory of Cancer Genomics and Department of Cell Biology, College of Basic Medical Sciences, Dalian Medical University, Dalian 116044, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Jia
mesh_terms: D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage* / Q000493:pharmacokinetics; D017209:Apoptosis / Q000187:drug effects*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D002470:Cell Survival / Q000187:drug effects; D005909:Glioblastoma / Q000188:drug therapy / Q000378:metabolism*; D008279:Magnetic Resonance Imaging / Q000379:methods; D051381:Rats; D000077185:Resveratrol; D050796:STAT3 Transcription Factor / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D013129:Spinal Puncture; D013267:Stilbenes / Q000008:administration & dosage* / Q000493:pharmacokinetics
chemical_list: D000972:Antineoplastic Agents, Phytogenic; D050796:STAT3 Transcription Factor; D013267:Stilbenes; D000077185:Resveratrol
keywords: STAT3 signaling; cell death; lumbar puncture; orthotopic rat glioblastoma; resveratrol