Abstract
PDCD5 (programmed cell death 5) accelerates apoptosis of certain tumor cells and is expressed at low levels in marrow-nucleated cells of AML and CML patients. In the present study, we evaluated the effects of PDCD5 overexpression on drug sensitivity of leukemia cells. K562 cells were treated with idarubicin (IDR) alone or in combination with adenoviral vectors expressing PDCD5 (Ad-PDCD5). As shown by annexin-V-FITC/PI dual labeling, apoptosis rates were markedly increased after combined treatment with Ad-PDCD5 compared to IDR treatment alone. We observed that PDCD5 overexpression significantly improves the antitumor effects of low dose IDR treatment in vivo. Tumor sizes were significantly decreased in combined Ad-PDCD5 and low dose IDR treatment groups compared with single IDR treatment groups. Similar results were obtained with combined systemic treatment of Ad-PDCD5 and low dose IDR, and combined treatment with Ad-PDCD5 local injection and low dose IDR i.p. injection. These results indicate that Ad-PDCD5 may be a promising agent for enhancing chemosensitivity.
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References
Hanahan D, Weinberg RA (2000) The hallmarks of cancer. Cell 100(1):57–70
Evan GI, Vousden KH (2001) Proliferation, cell cycle and apoptosis in cancer. Nature 411(6835):342–348
LaCasse EC, Baird S, Korneluk RG, MacKenzie AE (1998) The inhibitors of apoptosis (IAPs) and their emerging role in cancer. Oncogene 17(25):3247–3259
Miyake H, Hara I, Hara S, Arakawa S, Kamidono S (2000) Synergistic chemosensitization and inhibition of tumor growth and metastasis by adenovirus-mediated P53 gene transfer in human bladder cancer model. Urology 56(2):332–336
Tuve S, Racek T, Niemetz A, Schultz J, Soengas MS, Pützer BM (2006) Adenovirus-mediated TA-p73beta gene transfer increases chemosensitivity of human malignant melanomas. Apoptosis 11(2):235–243
Okumura K, Nakase M, Nakamura S, Kamei T, Inui M, Tagawa T (2007) Bax gene therapy for human osteosarcoma using cationic liposomes in vivo. Oncol Rep 17(4):769–773
Liu H, Wang Y, Zhang Y, Song Q, Di C, Chen G et al (1999) TFAR19, a novel apoptosis-related gene cloned from human leukemia cell line TF-1, could enhance apoptosis of some tumor cells induced by growth factor withdrawal. Biochem Biophys Res Commun 254(1):203–210
Zhang YM, Xu XZ, Liu HT, Song QS, Ma DL (2000) The apoptosis-accelerating effect of human recombinant TFAR19 protein on leukemia HL-60 cells. J Chin Immunol 16:8–11
Ruan GR, Chen SS, Chang Y, Fu JY, Wan H, Qin YZ et al (2002) Abnormality expression of a novel apoptosis-promoting molecule TFAR19 (PDCD5) in the bone marrow cells from adult chronic myeloid leukemia. J Peking Univ (Health Sci) 34:676–679
Ruan GR, Qin YZ, Chen SS, Li JL, Ma X, Chang Y et al (2006) Abnormal expression of the programmed cell death 5 gene in acute and chronic myeloid leukemia. Leuk Res 30(9):1159–1165
Wang Y, Li X, Wang L, Ding P, Zhang Y, Han W et al (2004) An alternative form of paraptosis-like cell death, triggered by TAJ/TROY and enhanced by PDCD5 overexpression. J Cell Sci 117(Pt 8):1525–1532
Chen Y, Douglass T, Jeffes EW, Xu Q, Williams CC, Arpajirakul N et al (2002) Living T9 glioma cells expressing membrane macrophage colony-stimulating factor produce immediate tumor destruction by polymorphonuclear leukocytes and macrophages via a “paraptosis”-induced pathway that promotes systemic immunity against intracranial T9 gliomas. Blood 100(4):1373–1380
Dal Canto MC, Gurney ME (1994) Development of central nervous system pathology in a murine transgenic model of human amyotrophic lateral sclerosis. Am J Pathol 145(6):1271–1279
Xu XR, Huang J, Xu ZG, Qian BZ, Zhu ZD, Yan Q et al (2001) Insight into hepatocellular carcinogenesis at transcriptome level by comparing gene expression profiles of hepatocellular carcinoma with those of corresponding noncancerous liver. Proc Natl Acad Sci USA 98(26):15089–15094
Hedenfalk I, Duggan D, Chen Y, Radmacher M, Bittner M, Simon R et al (2001) Gene-expression profiles in hereditary breast cancer. N Engl J Med 344(8):539–548
Liu ZH, Zhang D, Li KM, Liao QP (2004) Expression of PDCD5 in tissues of normal cervix, CIN I–III and cervical cancer. J Peking Univ (Health Sci) 36(4):407–410
Du Y, Hong T (2003) A preliminary study on the relationship between TF-1 cell apoptosis-related gene 19 and thyroid tumor. Chin J Intern Med 42:492–494
Yang YH, Zhao M, Li WM, Lu YY, Chen YY, Kang B et al (2006) Expression of programmed cell death 5 gene involves in regulation of apoptosis in gastric tumor cells. Apoptosis 11(6):993–1001
Ruan GR, Chen SS, Chang Y, Li JL, Qin YZ, Li LD et al (2007) Adenovirus-mediated PDCD5 gene transfer sensitizes apoptosis of K562 cells induced by etoposide. J Exp Hematol 15:936–940
Creutzig U, Körholz D, Niemeyer CM, Kabisch H, Graf N, Reiter A et al (2000) Toxicity and effectiveness of high-dose idarubicin during AML induction therapy: results of a pilot study in children. Klin Padiatr 212(4):163–168
Rockwell SC, Kallman RF, Fajardo LF (1972) Characteristics of a serially transplanted mouse mammary tumor and its tissue-culture-adapted derivative. J Natl Cancer Inst 49(3):735–749
Milas L, Raju U, Liao Z, Ajani J (2005) Targeting molecular determinants of tumor chemo-radioresistance. Semin Oncol 32(6 Suppl 9):S78–S81
Kohn KW, Pommier Y, Kerrigan D, Markovits J, Covey JM (1987) Topoisomerase II as a target of anticancer drug action in mammalian cells. NCI Monogr (4):61–71
Isaacs RJ, Davies SL, Wells NJ, Harris AL (1995) Topoisomerases II alpha and beta as therapy targets in breast cancer. Anticancer Drugs 6(2):195–211
Dartsch DC, Gieseler F (2007) Repair of idarubicin-induced DNA damage: a cause of resistance? DNA Repair (Amst) 6(11):1618–1628
Berger JM, Gamblin SJ, Harrison SC, Wang JC (1996) Structure and mechanism of DNA topoisomerase II. Nature 379(6562):225–232
Cheon J, Ko SC, Gardner TA, Shirakawa T, Gotoh A, Kao C et al (1997) Chemogene therapy: osteocalcin promoter-based suicide gene therapy in combination with methotrexate in a murine osteosarcoma model. Cancer Gene Ther 4(6):359–365
Nemunaitis J, Swisher SG, Timmons T, Connors D, Mack M, Doerksen L et al (2000) Adenovirus-mediated p53 gene transfer in sequence with cisplatin to tumors of patients with non-small-cell lung cancer. J Clin Oncol 18(3):609–622
Dong YB, Yang HL, Elliott MJ, McMasters KM (2002) Adenovirus-mediated E2F-1 gene transfer sensitizes melanoma cells to apoptosis induced by topoisomerase II inhibitors. Cancer Res 62(6):1776–1783
Ma X, Ruan G, Wang Y, Li Q, Zhu P, Qin YZ et al (2005) Two single-nucleotide polymorphisms with linkage disequilibrium in the human programmed cell death 5 gene 5’ regulatory region affect promoter activity and the susceptibility of chronic myelogenous leukemia in Chinese population. Clin Cancer Res 11(24 Pt 1):8592–8599
Chen Y, Sun R, Han W, Zhang Y, Song Q, Di C et al (2001) Nuclear translocation of PDCD5 (TFAR19): an early signal for apoptosis? FEBS Lett 509(2):191–196
Zou XJ, Peng JR, Zhong LJ, Lou YX, Liu D, Yang B et al (2006) Study on the interaction between PDCD5 and DNA Using MALDI-TOF-MS. J Chin Mass Spectrom Soc 27(suppl):179–180
Pai C, Wang A (2005) Structural study of DNA binding protein pdcd5 from sulfolobus solfataricus. Acta Cryst A 61:C224 (Abstr)
Acknowledgments
This study was supported by the grant from National Natural Science Foundation of China (No. 30670894) and supported in part by the grant from the National High Technology Research and Development Program of China (863 Program) (No. 2002BA711A01).
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Guo-Rui Ruan and Hong-Shan Zhao contributed equally to this work.
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Ruan, GR., Zhao, HS., Chang, Y. et al. Adenovirus-mediated PDCD5 gene transfer sensitizes K562 cells to apoptosis induced by idarubicin in vitro and in vivo. Apoptosis 13, 641–648 (2008). https://doi.org/10.1007/s10495-008-0206-9
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DOI: https://doi.org/10.1007/s10495-008-0206-9