[Inhibitory effect of bcl-2 antisense oligodeoxynucleotides on growth of human lung carcinoma xenograft in nude mice].
OBJECTIVE
Antisense oligodeoxynucleotides (ASODN) targeting bcl-2 have in vitro and in vivo antitumor activities. We have identified a novel antisense sequence in the coding region of bcl-2 mRNA that could enhance chemosensitivity and radiosensitivity of leukemia cells and lung carcinoma cells. This study was designed to investigate inhibitory effects of bcl-2 ASODN on development and growth ability of human lung carcinoma NCI-H460 cells xenograft in nude mice.


METHODS
bcl-2 ASODN was added to NCI-H460 cells. Inhibitory rate of cell growth was assayed by MTT assay. bcl-2 ASODN-treated NCI-H460 cells were implanted subcutaneously into nude mice to observe tumor growth and calculate tumor inhibitory rate. Seven days after subcutaneous implantation of untreated NCI-H460 cells, the tumor-bearing mice were randomized into 3 groups: control group, ASODN group, and nonsense oligodeoxynucleotides (NSODN) group. bcl-2 ASODN, bcl-2 NSODN, and saline were separately injected into the tumor bodies of mice in relevant groups for 3 week. The tumor weight and volume were measured, and the morphology of tumor cells was observed under microscope.


RESULTS
bcl-2 ASODN reduced the growth of NCI-H460 cells in a time-dependent manner. Inhibitory rate of NCI-H460 cells was significantly higher in bcl-2 ASODN group than in bcl-2 NSODN group (P<0.05). The tumorigenic ability of NCI-H460 cells was reduced by bcl-2 ASODN, with the maximum tumor growth inhibitory rate of 87.5% (P<0.01). The tumor formation time was prolonged to 12.6 days. Tumor growth was significantly inhibited in bcl-2 ASODN group as compared with that in NSODN group and control group(P<0.01). The tumor weight was significantly lighter in bcl-2 ASODN group than in bcl-2 NSODN group and control group (P<0.01). The growth inhibitory rate was 71.0% in bcl-2 ASODN group. Serious necrosis foci and inflammatory cell infiltration were observed in tumor tissues of bcl-2 ASODN group, while cancer cells were diffused in tumor tissues of bcl-2 NSODN group and control group.


CONCLUSIONS
bcl-2 ASODN can suppress tumorigenic ability of NCI-H460 cells and inhibit tumor growth in nude mice.
He
Dong-Mei
DM
Institute of Hematology, Medical College, Jinan University, Guangzhou, Guangdong 510632, P. R. China.
Zhang
Huan
H
D000818:Animals; D002289:Carcinoma, Non-Small-Cell Lung / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005260:Female; D019254:Genes, bcl-2; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D020319:Oligodeoxyribonucleotides, Antisense / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000235:genetics*
D020319:Oligodeoxyribonucleotides, Antisense; D019253:Proto-Oncogene Proteins c-bcl-2