title: Light-controlled inhibition of malignant glioma by opsin gene transfer.
abstract: Glioblastomas are aggressive cancers with low survival rates and poor prognosis because of their highly proliferative and invasive capacity. In the current study, we describe a new optogenetic strategy that selectively inhibits glioma cells through light-controlled membrane depolarization and cell death. Transfer of the engineered opsin ChETA (engineered Channelrhodopsin-2 variant) gene into primary human glioma cells or cell lines, but not normal astrocytes, unexpectedly decreased cell proliferation and increased mitochondria-dependent apoptosis, upon light stimulation. These optogenetic effects were mediated by membrane depolarization-induced reductions in cyclin expression and mitochondrial transmembrane potential. Importantly, the ChETA gene transfer and light illumination in mice significantly inhibited subcutaneous and intracranial glioma growth and increased the survival of the animals bearing the glioma. These results uncover an unexpected effect of opsin ion channels on glioma cells and offer the opportunity for the first time to treat glioma using a light-controllable optogenetic approach.
authors.affiliation: Shenzhen Key Lab of Neuropsychiatric Modulation, Research Centre for Neural Engineering, Shenzhen Institutes of Advanced Technology, Chinese Academy of Sciences, Xili Nanshan, Shenzhen, China.
authors.forename: F
authors.initials: F
authors.lastname: Yang
authors.forename: J
authors.initials: J
authors.lastname: Tu
authors.forename: J-Q
authors.initials: JQ
authors.lastname: Pan
authors.forename: H-L
authors.initials: HL
authors.lastname: Luo
authors.forename: Y-H
authors.initials: YH
authors.lastname: Liu
authors.forename: J
authors.initials: J
authors.lastname: Wan
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.forename: P-F
authors.initials: PF
authors.lastname: Wei
authors.forename: T
authors.initials: T
authors.lastname: Jiang
authors.forename: Y-H
authors.initials: YH
authors.lastname: Chen
authors.forename: L-P
authors.initials: LP
authors.lastname: Wang
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000235:genetics / Q000528:radiation effects; D015153:Blotting, Western; D002453:Cell Cycle / Q000235:genetics / Q000528:radiation effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000528:radiation effects; D002470:Cell Survival / Q000235:genetics / Q000528:radiation effects; D004594:Electrophysiology; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005910:Glioma / Q000235:genetics / Q000628:therapy*; D006801:Humans; D008027:Light; D053078:Membrane Potential, Mitochondrial / Q000235:genetics / Q000528:radiation effects; D051379:Mice; D008819:Mice, Nude; D055355:Opsins / Q000235:genetics / Q000502:physiology*
chemical_list: D055355:Opsins