期刊
ONCOLOGY RESEARCH
卷 20, 期 5-6, 页码 251-258出版社
COGNIZANT COMMUNICATION CORP
DOI: 10.3727/096504013X13589503483012
关键词
Autophagy; Breast cancer; Radioresistance; RNA interference
类别
资金
- National Natural Science Foundation of China [30900383]
- Doctoral Fund for Youth Scholars of Ministry of Education of China [20090142120051]
Hypoxia is a hallmark of solid tumors, which presents a major obstacle to the effectiveness of radiation therapy. However, the function and the importance of molecular response have not been well defined. In the present study, hypoxia-induced autophagy and its effect on the response of breast cancer cells to ionizing radiation were examined. Results showed that hypoxic exposure induced a marked accumulation of autophagosomes accompanied by mRNA induction of the autophagy-related genes Beclin-1, Atg5, Atg7, and Atg12. The elevated autophagic activity was associated with increased radioresistance of tumor cells. Accordingly, blockade of autophagy by pharmacological inhibition or Beclin-1 small interfering RNA (siRNA) contributed to retardation of DNA double-strand breaks (DSB) repair and significant radiosensitization. Our data indicate that strategies designed to suppress autophagic activity may represent promising new therapies for sensitizing hypoxic breast cancer cells to ionizing radiation (IR).
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