Enhancing cisplatin sensitivity in MCF-7 human breast cancer cells by down-regulation of Bcl-2 and cyclin D1.
MCF-7 human breast cancer cells are relatively resistant to cisplatin treatment compared to other breast cancer cell lines. In order to identify possible targets for sensitizing the breast cancer cells to cisplatin treatment protein expression levels and the phosphorylation status of 27 different signaling proteins were examined. MCF-7 cells expressed high levels of anti-apoptotic Bcl-2 protein relative to more cisplatin sensitive breast cancer cells. After cisplatin treatment a decrease in cyclin D1 was seen in all the breast cancer cells studied. Therefore, Bcl-2 and cyclin D1 were chosen as putative targets for increasing cell death and growth arrest induced by cisplatin, thereby enhancing the drug sensitivity in MCF-7. RNA interference, using Bcl-2- and cyclin D1- siRNAs sensitized MCF-7 cells to cisplatin treatment and by simultaneous knockdown of both Bcl-2 and cyclin D1 further sensitization was seen. This shows the potential of targeting both apoptotic- and cell cycle-regulating pathways to enhance the effect of chemotherapy.
Yde
Christina Westmose
CW
Institute of Biochemistry and Molecular Biology, University of Southern Denmark, DK-5230 Odense M, Denmark.
Issinger
Olaf-Georg
OG
D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism; D002453:Cell Cycle / Q000187:drug effects / Q000235:genetics; D045744:Cell Line, Tumor; D002945:Cisplatin / Q000494:pharmacology*; D019938:Cyclin D1 / Q000096:biosynthesis* / Q000235:genetics; D015536:Down-Regulation; D004354:Drug Screening Assays, Antitumor; D016193:G1 Phase / Q000187:drug effects / Q000235:genetics; D006801:Humans; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000096:biosynthesis* / Q000235:genetics; D034741:RNA, Small Interfering / Q000235:genetics; D014162:Transfection
D000970:Antineoplastic Agents; D019253:Proto-Oncogene Proteins c-bcl-2; D034741:RNA, Small Interfering; D019938:Cyclin D1; D002945:Cisplatin