Modification of the sensitivity to cisplatin with c-myc over-expression or down-regulation in colon cancer cells.
Human colon cancer SW480 cells express the c-myc gene. On the other hand, SW480DDP cell lines resistant to cisplatin exhibited decreased c-myc gene expression, but their cell growth rates remained similar to those of their parental cells. Antisense oligonucleotides to c-myc inhibited c-myc expression and induced increased resistance to cisplatin in SW480 cells. In contrast, SW480DDP cells showed increased c-myc expression and reversed sensitivity to cisplatin when these cells were transfected with c-myc cDNA from the pLNCX plasmid. Moreover, SW480DDP cells transfected with c-myc cDNA induced apoptosis when exposed to cisplatin, but not SW480 cells transfected with an antisense sequence for c-myc. Transfection either with a c-myc antisense sequence or c-myc cDNA to these cells did not change their growth rates. Thus enforced expression of c-myc in SW480 and SW620 lines sensitizes cells to cisplatin-induced apoptosis, whereas the down-regulation of c-myc in SW480DDP and SW620DDP increases cisplatin resistance when using antisense strategy.
Funato
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Division of Molecular Diagnostics, Department of Clinical Medicine, Tohoku University, School of Medicine, Sendai 980-8574, Japan. tfunato.cc.tohoku.ac.jp
Kozawa
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Kaku
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Sasaki
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D000230:Adenocarcinoma / Q000188:drug therapy* / Q000235:genetics; D000970:Antineoplastic Agents / Q000494:pharmacology*; D000972:Antineoplastic Agents, Phytogenic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects*; D002455:Cell Division / Q000187:drug effects; D002945:Cisplatin / Q000494:pharmacology*; D003110:Colonic Neoplasms / Q000188:drug therapy* / Q000235:genetics; D004249:DNA Damage / Q000187:drug effects; D017931:DNA Primers / Q000737:chemistry; D019008:Drug Resistance, Neoplasm; D005047:Etoposide / Q000494:pharmacology; D006801:Humans; D020287:In Situ Nick-End Labeling; D016376:Oligonucleotides, Antisense / Q000627:therapeutic use*; D016271:Proto-Oncogene Proteins c-myc / Q000235:genetics / Q000378:metabolism*; D012333:RNA, Messenger / Q000032:analysis / Q000235:genetics; D012334:RNA, Neoplasm / Q000032:analysis / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D014407:Tumor Cells, Cultured / Q000187:drug effects*
D000970:Antineoplastic Agents; D000972:Antineoplastic Agents, Phytogenic; D017931:DNA Primers; D016376:Oligonucleotides, Antisense; D016271:Proto-Oncogene Proteins c-myc; D012333:RNA, Messenger; D012334:RNA, Neoplasm; D005047:Etoposide; D002945:Cisplatin