[The effects of antisense oligonucleotides bcl-2/bcl-xl and bcl-2 on proliferation and apoptosis of breast cancer cells].
OBJECTIVE
To evaluate the effects of phosphorothioate antisense oligonucleotides (ASON) bcl-2/ bc-xl ASON and bcl-2 on the proliferation and apoptosis of breast cancer cells, MCF-7.


METHODS
1) bcl-2 ASON and bcl-2/bcl-xl ASON were transfected into MCF-7 cells with anionic long circulating liposomes (NA), cationic LCL (PA), respectively. 2) After incubation with bcl-2 ASON (FB1), bcl-2/bcl-xl ASON (FB2), NA loaded with bcl-2 ASON (NA-S) or bcl-2/bcl-xl ASON(NA-D), PA loaded with bcl-2 ASON(PA-S) or bcl-2/bc-xl ASON (PA-D) for 24 h, their inhibition on MCF-7 cells were evaluated by using HE staining, methythiazolyltetrazolium (MTT) and flow cytometry (FCM).


RESULTS
The significant difference of nuclear condensation, chromatin fragmentation and apoptotic bodies in MCF-7 cells, typical of apoptotic cell death was observed in groups of bcl-2/ bcl-xl bispecific ASON by compared with that of bcl-2 ASON treatment. The fluorensence intensities of bcl-2 in groups of NA-D and NA-S, PA-S and PA-D, FB1 and FB2 were 1.92+/-0.08 and 2.83+/-0.16 (P=0.028); 4.20+/-0.18 and 2.85+/-0.57 (P=0.001); 5.70+/-1.16 and 4.35+/-0.11 (P=0.001), respectively. The cell survival rates at 24 h of NA-D and NA-S, PA-S and PA-D, FB1 and FB2 were (0.32+/-0.03)% and (0.58+/-0.07)% (P=0.014); (0.71+/-0.03)% and (0.45+/-0.04)% (P=0.014); (0.88+/-0.04)% and (0.57+/- 0.05)% (P=0.003), respectively.


CONCLUSIONS
The bcl-2/bct-xl bispecific ASON could inhibit bcl-2 expression and induce apoptosis of breast cancer cells more efficiently than that treated with bcl-2 ASON alone.
Ma
Chao
C
Department of Nuclear Medicine, West China Hospital, Sichuan University, Chengdu, China.
Xie
Jia-Wei
JW
Kuang
An-Ren
AR
Huang
Rui
R
Tang
Gong-Shun
GS
D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy / Q000235:genetics / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D006801:Humans; D016376:Oligonucleotides, Antisense / Q000235:genetics / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics* / Q000378:metabolism; D014162:Transfection; D051020:bcl-X Protein / Q000235:genetics*
C494811:BCL2L1 protein, human; D016376:Oligonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2; D051020:bcl-X Protein