PMID- 22819929 OWN - NLM STAT- MEDLINE DCOM- 20130104 LR - 20181201 IS - 1872-6240 (Electronic) IS - 0006-8993 (Linking) VI - 1473 DP - 2012 Sep 14 TI - Low frequency and intensity ultrasound induces apoptosis of brain glioma in rats mediated by caspase-3, Bcl-2, and survivin. PG - 25-34 LID - 10.1016/j.brainres.2012.06.047 [doi] AB - 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. CI - Copyright (c) 2012 Elsevier B.V. All rights reserved. FAU - Zhang, Zhen AU - Zhang Z AD - Department of Ultrasound, China Medical University Affiliated First Hospital, Shenyang, Liaoning 110001, PR China. FAU - Chen, Jiang AU - Chen J FAU - Chen, Lufeng AU - Chen L FAU - Yang, Xianli AU - Yang X FAU - Zhong, Hongshan AU - Zhong H FAU - Qi, Xun AU - Qi X FAU - Bi, Yonghua AU - Bi Y FAU - Xu, Ke AU - Xu K LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't DEP - 20120720 PL - Netherlands TA - Brain Res JT - Brain research JID - 0045503 RN - 0 (Birc5 protein, rat) RN - 0 (Microtubule-Associated Proteins) RN - 0 (Proto-Oncogene Proteins c-bcl-2) RN - 0 (Survivin) RN - EC 3.4.22.- (Casp3 protein, rat) RN - EC 3.4.22.- (Caspase 3) SB - IM MH - Animals MH - Apoptosis/*physiology MH - Blotting, Western MH - Brain Neoplasms/*diagnostic imaging/ultrastructure MH - Caspase 3/*metabolism MH - Disease Models, Animal MH - Female MH - Fluorescent Antibody Technique MH - Glioma/*diagnostic imaging/ultrastructure MH - Immunohistochemistry MH - In Situ Nick-End Labeling MH - Microscopy, Electron, Transmission MH - Microtubule-Associated Proteins/*metabolism MH - Proto-Oncogene Proteins c-bcl-2/*metabolism MH - Rats MH - Rats, Wistar MH - Survivin MH - Ultrasonography EDAT- 2012/07/24 06:00 MHDA- 2013/01/05 06:00 CRDT- 2012/07/24 06:00 PHST- 2011/12/28 00:00 [received] PHST- 2012/06/10 00:00 [revised] PHST- 2012/06/28 00:00 [accepted] PHST- 2012/07/24 06:00 [entrez] PHST- 2012/07/24 06:00 [pubmed] PHST- 2013/01/05 06:00 [medline] AID - S0006-8993(12)01133-X [pii] AID - 10.1016/j.brainres.2012.06.047 [doi] PST - ppublish SO - Brain Res. 2012 Sep 14;1473:25-34. doi: 10.1016/j.brainres.2012.06.047. Epub 2012 Jul 20.