논문검색
Author Eun Jung Kim, In Mi Ji, Ki Jung Ahn, Eun Kyung Choi, Heon Jin Park, Byung Uk Lim, Chang W. Song, Heon Joo Park
Place of duty 1Department of Microbiology, College of Medicine, Inha University, Incheon, Korea, 2Department of Therapeutic Radiology, College of Medicine, University of Ulsan, Seoul, Korea, 3Department of Statistics College of Medicine, Inha University, Incheon, Korea, 4Radiobiology Laboratory, Department of Therapeutic Radiology, University of Minnesota Medical School, Minneapolis, MN, USA, 5Department of Radiation Oncology, College of Medicine, Inje University, Busan, Korea.
Title Synergistic Effect of Ionizing Radiation and beta-lapachone against RKO Human Colon Adenocarcinoma Cells
Publicationinfo Cancer Res Treat. 2005 Jun; 037(03): 183-190.
Key_word beta-Lapachone,Ionizing radiation,NQO1,RKO cells,Radiosensitization
Full-Text
Abstract Purpose: To reveal the interaction between beta-Lapachone (beta-lap) and ionizing radiation in causing cell death in RKO human colon adenocarcinoma cells, and to elucidate the potential usefulness of combined beta-lap treatment and radiotherapy for cancer treatment. Materials and Methods: The cytotoxicities of various treatments were determined in vitro using clonogenic and apoptotic cell death. The changes in cell cycle distribution were studied using flow cytometry and an in vitro kinase assay. The tumor growth was studied using RKO tumors grown s.c. in the hind leg BALB/c- nuslc nude mice. Results: beta-lap caused clonogenic cell death and rapid apoptosis in RKO cells in vitro, in a dose dependent manner. The repair of sublethal radiation damage was almost completely inhibited when cells were maintained in beta-lap during the interval between the two-dose irradiation. Flow cytometry study demonstrated that beta-lap induced apoptosis, independent of the cell cycle phase, and completely prohibited the induction of radiation- induced G2 arrest in irradiated cells. The prohibition of radiation-induced G2 arrest is unclear, but may be related to the profound suppression of the p53, p21 and cyclin B1-Cdc2 kinase activities observed in cells treated with beta-lap. The combination of beta-lap and radiation markedly enhanced the radiation-induced growth suppression of tumors. Conclusion: beta-lap is cytotoxic against RKO cells, both in vitro and in vivo, and also sensitized cells to ionizing radiation by inhibiting sublethal radiation damage repair. beta-lap is potentially useful as a potent anti-cancer chemotherapy drug and potent radiosensitizer against caner cells. (Cancer Res Treat. 2005;37:183-190)