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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 발행연도
- 2008.1
- 수록면
- 118 - 129 (12page)
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Proton beam is useful to target tumor tissue sparing normal cels by alowing precise dose only into tumor cells. However, the cellular and molecular mecha-nisms by which proton beam induces tumor cell death are still undefined. We irradiated three different tumor cells (LLC, HepG2, and Molt-4) with low energy proton beam (35 MeV) with spread out Bragg peak (SOBP) in vitro, and investigated cell death by MT or CCK-8 as-say at 24 h after irradiation. LLC and HepG2 cells were sensitive to proton beam at over 10 Gy to induce apop-Relative biological effectiveness (RBE) values for the death rate relative to γ-ray were ranged from 1.1 to 2.3 in LLC and HepG2 but from 0.3 to 0.7 in Molt-4 at 1 d after irradiation by colony formation assay. The typical apoptotic nuclear DNA morphological pattern was ob-served by staining with 4'-6-diamidino-2-phenylindole (DAPI). Tiny fragmented DNA was observed in HepG2 but not in Molt-4 by the treatment of proton in apoptotic with FITC-Annexin-V, early as well as median apoptotic fractions were clearly increased by proton treatment. Proton beam-iradiated tumor cells induced a cleavage of poly (ADP-ribose) polymerase-1 (PARP-1) and pro-caspases-3 and -9. Activity of caspases was highly en-hanced after proton beam iradiation. Reactive oxygen species (ROS) were significantly increased and N-ace-tyl cysteine pretreatment restored the apoptotic cell death induced by proton beam. Furthermore, p38 and nant negative mutants of p38 and JNK revived pro-ton-induced apoptosis, suggesting that p38 and JNK pathways may be activated through ROS to activate apoptosis. In conclusion, our data clearly showed that single treatment of low energy proton beam with SOBP increased ROS and induced cell death of solid tumor cells (LLC and HepG2) in an apoptotic cell death pro-gram by the induction of caspases activities.
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참고문헌 (25)
참고문헌 신청
Belli M / 1989 / RBE-LET relationship for survival of V79 cells irradiated with low energy protons / Int J Rad Biol 55 : 93 ~ 104
Belli M / 1998 / Simone G, Tabocchini MA, Tiveron P. RBE-LET relationship for cell inactivation and mutation induced by low energy protons in V79 cells: further results at th
Belli M / 2000 / Inactivation of human normal and tumour cells irradiated with low energy protons / Int J Radiat Biol 76 : 831 ~ 9
Benhar M / 2001 / Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensi
Benhar M / 2002 / ROS, stress-activated kinases and stress signaling in cancer / EMBO Rep 3 : 420 ~ 5
Belli M / 1998 / Simone G, Tabocchini MA, Tiveron P. RBE-LET relationship for cell inactivation and mutation induced by low energy protons in V79 cells: further results at th
Belli M / 2000 / Inactivation of human normal and tumour cells irradiated with low energy protons / Int J Radiat Biol 76 : 831 ~ 9
Benhar M / 2001 / Enhanced ROS production in oncogenically transformed cells potentiates c-Jun N-terminal kinase and p38 mitogen-activated protein kinase activation and sensi
Benhar M / 2002 / ROS, stress-activated kinases and stress signaling in cancer / EMBO Rep 3 : 420 ~ 5
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