Abstract | PURPOSE:
Clusterin plays important roles in cell survival and death. Inactivation of clusterin enhances the therapeutic efficacy of chemotherapy in lung cancer models. The purpose of this study was to determine whether inhibition of clusterin by an antisense-based investigative drug enhances radiation sensitization in a lung cancer model. METHODS AND MATERIALS: RESULTS:
OGX-011 specifically attenuated the expression of secreted clusterin (prosurvival), with no apparent effect on the expression of nuclear clusterin (proapoptotic). Apoptosis was significantly increased when H460 lung cancer cells were treated with OGX-011 plus radiation. Inhibition of clusterin followed by radiation greatly decreased cell survival. H460 xenografts that were treated with OGX-011 plus radiotherapy demonstrated growth delay beyond 17 days. Doppler studies showed that tumor blood flow was compromised when mice bearing H460 xenografts were treated with OGX-011 and radiation. CONCLUSION:
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Authors | Carolyn Cao, Eric T Shinohara, Hecheng Li, Ken J Niermann, Kwang Woon Kim, Konjeti R Sekhar, Martin Gleave, Michael Freeman, Bo Lu |
Journal | International journal of radiation oncology, biology, physics
(Int J Radiat Oncol Biol Phys)
Vol. 63
Issue 4
Pg. 1228-36
(Nov 15 2005)
ISSN: 0360-3016 [Print] United States |
PMID | 16253777
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't, Research Support, U.S. Gov't, Non-P.H.S.)
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Chemical References |
- Clusterin
- Neoplasm Proteins
- OGX-011
- Oligonucleotides, Antisense
- Thionucleotides
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Topics |
- Animals
- Apoptosis
- Cell Line, Tumor
- Clusterin
(antagonists & inhibitors)
- Female
- Humans
- Lung Neoplasms
(blood supply, drug therapy, radiotherapy)
- Mice
- Mice, Nude
- Neoplasm Proteins
(antagonists & inhibitors)
- Oligonucleotides, Antisense
(therapeutic use)
- Thionucleotides
(therapeutic use)
- Transfection
- Transplantation, Heterologous
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