Chemosensitization of breast carcinoma cells with the use of bcl-2 antisense oligodeoxynucleotide.
This study was designed to observe whether the rates of apoptosis induced in the breast cancer cell line MCF-7 by 5-fluorouracil (5-FU) could be enhanced by transfecting bcl-2 antisense oligonucleotide (ASODN). In our experiment, bcl-2 ASODNs and control ODNs including untreated control, sense ODN and scrambled ODN, were transfected into MCF-7 cells. Changes in expression of the bcl-2 gene were examined by Western blot; cell growths were detected by MTT assay, and apoptosis rates were detected by flow cytometry (FCM). Expression of bcl-2 protein after transfection of bcl-2 ASODN was significantly lower than control ODNs. Moreover, incubation of MCF-7 with bcl-2 ASODN prior to 5-FU treatment caused remarkable loss of viable cells compared with all other control ODNs (P < 0.01). FCM showed the apoptosis rates for ASODN, untreated control, sense ODN and scrambled ODN (29.8 +/- 7.4)%, (8.0 +/- 2.3)%, (15.0 +/- 5.1)% and (16.5 +/- 7.1)%, respectively. Compared with control ODNs, ASODN achieved the strongest effect in terms of enhancing apoptosis (P < 0.01). These results suggest that combining bcl-2 ASODN with 5-FU led to synergistic cytotoxicity.
Yang
J H
JH
Department of General Surgery, Shidong Hospital, Teaching Hospital of Shanghai, Second Medical University, Shidong Hospital, Shanghai 200090, China. yangjianhuicn@hotmail.com
Feng
F
F
Qian
H
H
Cheng
H
H
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor / Q000187:drug effects; D005260:Female; D005434:Flow Cytometry; D005472:Fluorouracil / Q000494:pharmacology*; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism
D000964:Antimetabolites, Antineoplastic; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D005472:Fluorouracil