[Inhibitory effect of bcl-2 antisense oligodeoxynucleotides on growth of human lung carcinoma xenograft in nude mice]

Abstract

Background & 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.

Conclusion: bcl-2 ASODN can suppress tumorigenic ability of NCI-H460 cells and inhibit tumor growth in nude mice.