c-myc antisense oligonucleotides sensitize human colorectal cancer cells to chemotherapeutic drugs.
作者： Mohamed-Salah I. Abaza , Amal Al-Saffar , Shorooq Al-Sawan , Rajaa Al-Attiyah
DOI: 10.1159/000156706
关键词:
摘要: Background/Aims: Overexpression of the c-myc oncogene frequently occurs in both colon tumors and carcinoma cell lines. We examined sensitization human colorectal cancer cells to chemotherapeutic drugs using antisense (AS) phosphorothioate oligonucleotides ([S]ODNs). Methods: Cancer were treated with [S]ODNs, taxol, 5-fluorouracil (5-FU), doxorubicin vinblastine individually combination. The antiproliferative effects, type interaction between [S]ODNs cytotoxic drugs, cycle, apoptosis expression cell-cycle- apoptosis-regulatory genes evaluated. Results: After treatment withc-myc AS[S]ODNs, growth was markedly inhibited a dose- time-dependent manner levels mRNA protein greatly decreased (p myc AS[S]ODNs or by combination arrested G2/M S phases. treatments also exhibited marked apoptotic effect compared single treatments. AS[S]ODN reduced Bcl2, BclxL, cdk2, cyclin E1, cdk1 B1, while increasing p21, p27, bax caspase-3. Conclusion: This two-hit approach may be important quest overcome drug resistance patients whose carry an overexpressed gene.
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