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Comparison of effects of antisense bcl-2, IL-6 and IL-6R oligodeoxynucleotides on smallcell lung cancer NCIH446 cells
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Abstract:
Objective:To compare the effects of antisense (AS) bcl2, interleukin6（IL6） and interleukin6 receptor phosphorothioate oligodeoxynucleotides (PSODN) on the proliferation and apoptosis of smallcell lung cancer NCIH446 cells, and to explore strategies of target genes selection in antisense oligodeoxynucleotides therapy. Methods:Bcl2 ASPSODN, IL6 ASPSODN and IL6R ASPSODN were synthesized and were used to treat NCIH446 cells. Proliferation and viability of NCIH446 cells were measured by cel1 clone formation assay after treatment; apoptosis of NCIH446 cells was detected by DNA content analysis and MitoCapture detection kit; and the expression of bcl2, IL6 and IL6R mRNA was examined by RTPCR. Results: （1）All the three antisense phosphorothioate oligodeoxynucleotides IL6, bcl2, IL6R ASPSODN inhibited proliferation and viability of lung cancer NCIH446 cells, and induced NCIH446 cells apoptosis, with the inhibitory effect of IL6 ASPSODN more effective than those of bcl2 ASPSODN and IL6R ASPSODN. （2）All the three kinds of ASPSODN decreased the corresponding gene expression, with gene expression decreased by (84.1±5.01)%, (62.6±3.42)% and (60.3±4.45)% in IL6, bcl2 and IL6R ASPSODN group, respectively. （3）ASPSODN not only inhibited the expression of its target gene, but also regulated expression of other genes. IL6 ASPSODN decreased bcl2 expression by (32.2±0.20)% and bcl2 ASPSODN increased IL6 expression by (74.3±413)%. Conclusion: IL6 ASPSODN is more effective than bcl2 and IL6R ASPSODN in inducing apoptosis of smallcell lung cancer NCIH446 cells, so IL6 may be used as a target gene in antisense oligodeoxynucleotide therapy of smallcell lung cancer.
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Project Supported:
Supported by the Research Foundation for Young Scholars of Fujian Province(No.200403）
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