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- 2013.1
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Radiation and drug resistance remain the major challenges and causes of mortality in the treatment of locally advanced,recurrent and metastatic breast cancer. Dysregulation of phospholipase D (PLD) has been found in several human cancers and is associated with resistance to anticancer drugs. In the present study, we evaluated the effects of PLD inhibition on cell survival, cell death and DNA damage after exposure to ionizing radiation (IR). Combined IR treatment and PLD inhibition led to an increase in the radiation-induced apoptosis of MDA-MB-231 metastatic breast cancer cells. The selective inhibition of PLD1and PLD2 led to a significant decrease in the IR-induced colony formation of breast cancer cells. Moreover, PLD inhibition suppressed the radiation-induced activation of extracellular signal-regulated kinase and enhanced the radiation-stimulated phosphorylation of the mitogen-activated protein kinases p38 and c-Jun N-terminal kinase. Furthermore, PLD inhibition, in combination with radiation, was very effective at inducing DNA damage, when compared with radiation alone. Taken together,these results suggest that PLD may be a useful target molecule for the enhancement of the radiotherapy effect.
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참고문헌 (24)
참고문헌 신청
Avila MA / 1993 / Activation of phospholipase D participates in signal transduction pathways responsive to gamma-radiation / Cancer Res 1 : 4474 ~ 4476
Candelaria M / 2006 / Radiosensitizers in cervical cancer: cisplatin and beyond / Radiat Oncol 1 : 15 ~ 31
Gozgit JM / 2007 / PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phosphor-Akt-negative breast carcinomas / Br J Cancer 97 : 809 ~ 817
Haber JE / 2000 / Partners and pathways repairing a double-strand break / Trends Genet 16 : 259 ~ 264
Haykal J / 2009 / The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloro-quinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells / Radiat Oncol 4 : 25 ~ 34
Candelaria M / 2006 / Radiosensitizers in cervical cancer: cisplatin and beyond / Radiat Oncol 1 : 15 ~ 31
Gozgit JM / 2007 / PLD1 is overexpressed in an ER-negative MCF-7 cell line variant and a subset of phosphor-Akt-negative breast carcinomas / Br J Cancer 97 : 809 ~ 817
Haber JE / 2000 / Partners and pathways repairing a double-strand break / Trends Genet 16 : 259 ~ 264
Haykal J / 2009 / The radiosensitizer 2-benzoyl-3-phenyl-6,7-dichloro-quinoxaline 1,4-dioxide induces DNA damage in EMT-6 mammary carcinoma cells / Radiat Oncol 4 : 25 ~ 34
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