title: Low frequency and intensity ultrasound induces apoptosis of brain glioma in rats mediated by caspase-3, Bcl-2, and survivin.
abstract: Low frequency and intensity ultrasound (LFU) sonication can selectively induce brain tumor cell apoptosis without damaging neural cells, while also enhancing drug delivery to brain tumors. To explore the underlying mechanisms of related pathways in LFU-induced apoptosis, we investigated the expression of proteins associated with LFU-induced apoptosis. C6 cells were used for in vitro experiments and C6 tumor-bearing rats were used during in vivo experiments. 3-[4.5-Dimethylthiazol-2-yl]-2,5-diphenyltetrazolium bromide; thiazolyl blue (MTT) assay was used to detect C6 cell viability in vitro. Terminal deoxynucleotidyl transferase-mediated dUTP nick end labeling (TUNEL) analysis was used to check the apoptotic cells, and they were counted and analyzed both in vitro and in vivo. Transmission electron microscopy (TEM) was used to illustrate the ultrastructure of apoptotic nuclei of cancer cells in vivo. The expressions of caspase-3, Bcl-2, and survivin proteins were assessed by immunofluorescence, immunohistochemistry and Western blot analysis in vivo. C6 cell viability decrease was statistically significant; the numbers of apoptotic C6 cells in the LFU sonication groups were higher than those in the control group both in vitro and in vivo. The expression of caspase-3 increased, yet the expressions of Bcl-2 and survivin decreased significantly 6h after LFU sonication, compared with the control group in vivo. This study suggests that LFU can induce apoptosis in vitro and in vivo, and that three signaling proteins, caspase-3, Bcl-2, and survivin, might be involved in LFU-induced apoptosis.
authors: Department of Ultrasound, China Medical University Affiliated First Hospital, Shenyang, Liaoning 110001, PR China.
authors: Zhen
authors: Z
authors: Zhang
authors: Jiang
authors: J
authors: Chen
authors: Lufeng
authors: L
authors: Chen
authors: Xianli
authors: X
authors: Yang
authors: Hongshan
authors: H
authors: Zhong
authors: Xun
authors: X
authors: Qi
authors: Yonghua
authors: Y
authors: Bi
authors: Ke
authors: K
authors: Xu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D015153:Blotting, Western; D001932:Brain Neoplasms / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D053148:Caspase 3 / Q000378:metabolism*; D004195:Disease Models, Animal; D005260:Female; D005455:Fluorescent Antibody Technique; D005910:Glioma / Q000000981:diagnostic imaging* / Q000648:ultrastructure; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D046529:Microscopy, Electron, Transmission; D008869:Microtubule-Associated Proteins / Q000378:metabolism*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism*; D051381:Rats; D017208:Rats, Wistar; D000077022:Survivin; D014463:Ultrasonography
chemical_list: C516989:Birc5 protein, rat; D008869:Microtubule-Associated Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D000077022:Survivin; C505410:Casp3 protein, rat; D053148:Caspase 3