[A novel bcl-2 antisense oligodeoxynucleotide F951 increases sensitivity of HL-60 cells to Ara-C].
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.
Li
Dong-Liang
DL
Fujian Institute of Hematology, The Affiliated Union Hospital, Fujian Medical University, Fuzhou 350001, China.
Lu
Lian-Huang
LH
Chen
Ying-Yu
YY
Lin
Zhen-Xing
ZX
D000964:Antimetabolites, Antineoplastic / Q000494:pharmacology; D017209:Apoptosis / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D003561:Cytarabine / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004357:Drug Synergism; D005434:Flow Cytometry; D018922:HL-60 Cells; D006801:Humans; D020319:Oligodeoxyribonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000964:Antimetabolites, Antineoplastic; D020319:Oligodeoxyribonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; D003561:Cytarabine