目的: 比较bcl2、白介素6（interleukin6，IL6）、白介素6受体(interleukin6 receptor，IL6R)反义硫代磷酸寡脱氧核苷酸（antisense phosphorothiate oligodeoxynucleotide, ASPSODN)对小细胞肺癌细胞株NCIH446细胞增殖及诱导凋亡的作用，初步探讨反义核苷酸技术治疗中靶基因的选择策略。方法：合成反义寡脱氧核苷酸bcl2 ASPSODN、IL6 ASPSODN、IL6R ASPSODN，分别作用于NCIH446细胞株,通过细胞克隆形成实验检测细胞增殖活性的变化，细胞凋亡线粒体流式检测及DNA倍体分析检测细胞凋亡，半定量RTPCR检测相关基因表达水平的变化。结果：（1）bcl2 ASPSODN、IL6 ASPSODN、IL6R ASPSODN均能够抑制肺癌细胞增殖活性和诱导细胞凋亡，其中以IL6 ASPSODN抑制作用最强， bcl2 ASPSODN次之， IL6R ASPSODN作用最弱。（2）3种反义寡脱氧核苷酸均能下调肺癌细胞相应基因的表达水平，其中以IL6下调幅度最大，达(84.1±5.01）%; bcl2和IL6R基因下调幅度相近，分别为(62.6±3.42）%和(60.3±4.45）%。（3）反义核苷酸作用后除了引起自身基因表达下调外，还伴对其他基因表达的调节作用，如IL6 ASPSODN作用使bcl2基因表达下调(32.2±020）%；而bcl2 ASPSODN作用使IL6基因表达上调(74.3±413）%。 结论：IL6 ASPSODN较bcl2 ASPSODN和IL6R ASPSODN能更有效地诱导小细胞肺癌细胞凋亡，IL6是NCIH446小细胞肺癌反义核苷酸治疗较为合适的靶基因。

Objective:To compare the effects of antisense (AS) bcl2, interleukin6（IL6） and interleukin6 receptor phosphorothioate oligodeoxynucleotides (PSODN) on the proliferation and apoptosis of smallcell lung cancer NCIH446 cells, and to explore strategies of target genes selection in antisense oligodeoxynucleotides therapy. Methods:Bcl2 ASPSODN, IL6 ASPSODN and IL6R ASPSODN were synthesized and were used to treat NCIH446 cells. Proliferation and viability of NCIH446 cells were measured by cel1 clone formation assay after treatment; apoptosis of NCIH446 cells was detected by DNA content analysis and MitoCapture detection kit; and the expression of bcl2, IL6 and IL6R mRNA was examined by RTPCR. Results: （1）All the three antisense phosphorothioate oligodeoxynucleotides IL6, bcl2, IL6R ASPSODN inhibited proliferation and viability of lung cancer NCIH446 cells, and induced NCIH446 cells apoptosis, with the inhibitory effect of IL6 ASPSODN more effective than those of bcl2 ASPSODN and IL6R ASPSODN. （2）All the three kinds of ASPSODN decreased the corresponding gene expression, with gene expression decreased by (84.1±5.01)%, (62.6±3.42)% and (60.3±4.45)% in IL6, bcl2 and IL6R ASPSODN group, respectively. （3）ASPSODN not only inhibited the expression of its target gene, but also regulated expression of other genes. IL6 ASPSODN decreased bcl2 expression by (32.2±0.20)% and bcl2 ASPSODN increased IL6 expression by (74.3±413)%. Conclusion: IL6 ASPSODN is more effective than bcl2 and IL6R ASPSODN in inducing apoptosis of smallcell lung cancer NCIH446 cells, so IL6 may be used as a target gene in antisense oligodeoxynucleotide therapy of smallcell lung cancer.

福建省卫生厅青年科研基金（No.200403）