A novel bcl-2 antisense oligodeoxynucleotide F951 increases sensitivity of HL-60 cells to Ara-C.
- Author:
Dong-Liang LI
1
;
Lian-Huang LU
;
Ying-Yu CHEN
;
Zhen-Xing LIN
Author Information
1. Fujian Institute of Hematology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, China.
- Publication Type:Journal Article
- MeSH:
Antimetabolites, Antineoplastic;
pharmacology;
Apoptosis;
drug effects;
Cell Proliferation;
drug effects;
Cytarabine;
pharmacology;
Dose-Response Relationship, Drug;
Drug Synergism;
Flow Cytometry;
HL-60 Cells;
Humans;
Oligodeoxyribonucleotides, Antisense;
genetics;
pharmacology;
Proto-Oncogene Proteins c-bcl-2;
genetics;
metabolism;
RNA, Messenger;
genetics;
metabolism;
Reverse Transcriptase Polymerase Chain Reaction
- From:
Journal of Experimental Hematology
2004;12(6):752-756
- CountryChina
- Language:Chinese
-
Abstract:
To investigate whether F951, a novel bcl-2 antisense oligodeoxynucleotide, increases the sensitivity of HL-60 cells to Ara-C, HL-60 cells were cultured with F951 in different doses alone or with F951 combined with low-dose Ara-C; the proliferation of HL-60 cells was assayed by MTT and trypan blue exclusion test; expression of Bcl-2 protein and its mRNA were measured by FACS and RT-PCR, respectively; the apoptotic cells were detected by DNA ladder and TUNEL assay. The results showed that F951 combined with low dose Ara-C revealed stronger effects in the aspects of inhibiting the HL-60 cells proliferation than in different doses of F951 alone or Ara-C alone. HL-60 cells treated with F951 + Ara-C had significantly lower trypan blue exclusion rate than that treated with Ara-C alone. The inhibition rates of HL-60 cells treated with FNS, Ara-C, F951 and F951 + Ara-C were -2.8%, 27.63%, 37.66%, 57.24%, respectively. F951 significantly down-regulated the expression of bcl-2 mRNA and protein in HL-60 cells. HL-60 cells treated with F951 + Ara-C showed more apparent DNA ladder and more apoptotic cells. It is concluded that F951 can inhibit bcl-2 gene expression and enhance the cytotoxicity of Ara-C through promoting apoptosis in HL-60 cells, hence increases the antitumor effect of Ara-C.
