Alteration of gene expression in melanoma cells following combined treatment with E2F-1 and doxorubicin.
BACKGROUND
The combination of E2F-1 gene therapy and chemotherapy produces a synergistic effect on melanoma cell apoptosis. However, the molecular mechanisms have not been fully elucidated. The purpose of this study was to identify novel genes or pathways that may play key roles in apoptosis when E2F-1 gene therapy is combined with doxorubicin chemotherapy.


METHODS
SK-MEL-2 melanoma cells were infected with Ad-E2F-1 alone, Ad-E2F-1 plus doxorubicin, or Ad-LacZ plus doxorubicin. After 16 hours of treatment, the total RNA was extracted from these cells and subjected to microarray analysis. Quantitative real-time PCR was performed to confirm the microarray data.


RESULTS
Our results showed that the combination treatment of Ad-E2F-1 and doxorubicin affected the expression of cytokines, transcription factors, as well as genes involved in signal transduction, cell cycle regulation and apoptosis.


CONCLUSIONS
Our findings have identified, for the first time, novel molecular targets and pathways that led to apoptosis in melanoma cells when Ad-E2F-1 was combined with doxorubicin. The molecular information provided here will enhance further mechanistic studies.
Hao
Hongying
H
Department of Surgery, University of Louisville School of Medicine, Louisville, KY 40292, USA.
Dong
Yan Bin
YB
Bowling
Maria T
MT
Zhou
H Sam
HS
McMasters
Kelly M
KM
D000256:Adenoviridae / Q000235:genetics; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D045744:Cell Line, Tumor; D003131:Combined Modality Therapy; D004317:Doxorubicin / Q000494:pharmacology*; D050687:E2F1 Transcription Factor / Q000235:genetics*; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects / Q000235:genetics; D015316:Genetic Therapy / Q000379:methods*; D006801:Humans; D008545:Melanoma / Q000188:drug therapy / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D020411:Oligonucleotide Array Sequence Analysis; D016133:Polymerase Chain Reaction
D000903:Antibiotics, Antineoplastic; D050687:E2F1 Transcription Factor; C493753:E2F1 protein, human; D004317:Doxorubicin