Systemic tumor suppression by the proapoptotic gene bik.
Metastatic breast cancer requires systemic treatment. We have developed a systemic gene therapy approach for breast cancer, consisting of a nonviral gene delivery system (SN) and a proapoptotic gene, bik. The transfection efficiency of SN carrying a reporter gene was 5-10 times higher than the common nonviral agents Fugene-6 and Lipofectamine in the presence of serum. The SN-bik gene complex induced significant apoptosis in four breast cancer cell lines in vitro as well as in orthotopic tumor tissues in nude mice. Systemically administrated SN-bik significantly inhibited the growth and metastasis of human breast cancer cells implanted in nude mice and prolonged the life span of the treated animals. This study demonstrates that SN-bik is a promising approach for further development as a potential therapeutic agent of cancer.
Zou
Yiyu
Y
Department of Molecular and Cellular Oncology, The University of Texas M. D. Anderson Cancer Center, Houston, Texas 77030, USA.
Peng
Hua
H
Zhou
Binhua
B
Wen
Yong
Y
Wang
Shao-Chun
SC
Tsai
Eing-Mei
EM
Hung
Mien-Chie
MC
D000818:Animals; D017209:Apoptosis / Q000235:genetics*; D051017:Apoptosis Regulatory Proteins; D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology / Q000628:therapy*; D002289:Carcinoma, Non-Small-Cell Lung / Q000235:genetics / Q000473:pathology / Q000628:therapy; D002412:Cations; D002455:Cell Division / Q000235:genetics; D004247:DNA / Q000008:administration & dosage* / Q000235:genetics; D005260:Female; D015316:Genetic Therapy / Q000379:methods*; D049452:Green Fluorescent Proteins; D008081:Liposomes / Q000008:administration & dosage; D008164:Luminescent Proteins / Q000096:biosynthesis / Q000235:genetics; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology / Q000628:therapy; D008565:Membrane Proteins; D051379:Mice; D008819:Mice, Nude; D024101:Mitochondrial Proteins; D014176:Protein Biosynthesis; D011506:Proteins / Q000235:genetics* / Q000502:physiology; D014162:Transfection; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays
D051017:Apoptosis Regulatory Proteins; C096820:BIK protein, human; D002412:Cations; D008081:Liposomes; D008164:Luminescent Proteins; D008565:Membrane Proteins; D024101:Mitochondrial Proteins; D011506:Proteins; D049452:Green Fluorescent Proteins; D004247:DNA