Chemosensitization of tumor cells: inactivation of nuclear factor-kappa B associated with chemosensitivity in melanoma cells after combination treatment with E2F-1 and doxorubicin.
Combination chemotherapy has been shown to be more effective than single-agent therapy for many types of cancer, but both are known to induce drug resistance in cancer cells. Two major culprits in the development of this drug resistance are nuclear factor-kappaB (NF-kappaB) and the multidrug resistance (MDR) gene. For this reason, chemogene therapy is emerging as a viable alternative to conventional chemotherapy combinations. We have shown that transduction of the E2F-1 gene in melanoma cells markedly increases cell sensitivity to doxorubicin, thereby producing a synergistic effect on melanoma cell apoptosis. Our microarray results show that the NF-kappaB pathway and related genes undergo significant changes after the combined treatment of E2F-1 and doxorubicin. In fact, inactivation of NF-kappaB is associated with melanoma cell apoptosis induced by E2F-1 and doxorubicin, providing a link between the NF-kappaB signaling pathway and the chemosensitivity of melanoma cells after this treatment.
Hao
Hongying
H
Surgical Oncology, University of Louisville, Louisville, KY, USA.
Zhou
H Sam
HS
McMasters
Kelly M
KM
D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004247:DNA / Q000378:metabolism; D004317:Doxorubicin / Q000627:therapeutic use*; D004354:Drug Screening Assays, Antitumor / Q000379:methods*; D050687:E2F1 Transcription Factor / Q000235:genetics* / Q000627:therapeutic use; D024202:Electrophoretic Mobility Shift Assay; D020868:Gene Silencing; D017930:Genes, Reporter; D015316:Genetic Therapy; D006801:Humans; D008156:Luciferases / Q000378:metabolism; D008545:Melanoma / Q000188:drug therapy* / Q000235:genetics*; D016328:NF-kappa B / Q000235:genetics* / Q000378:metabolism; D010957:Plasmids / Q000235:genetics; D011485:Protein Binding; D014158:Transcription, Genetic; D014162:Transfection
D050687:E2F1 Transcription Factor; D016328:NF-kappa B; D004317:Doxorubicin; D004247:DNA; D008156:Luciferases