[Experimental study of antisense oligodeoxynucleotide targeting survivin gene for cisplatin resistant human lung adeno-carcinoma xenograft in nude mice].

OBJECTIVE: To explore the feasibility of antisense oligodeoxynucleotide (ASODN) targeting survivin gene for cisplatin resistant human lung adeno-carcinoma xenograft in nude mice.

METHODS: Cisplatin resistant cell lines A549/CDDP were cultured routinely with RPMI1640 medium. A549/CDDP cells were subcutaneously implanted in nude mice to establish cisplatin resistant xenograft animal models. After survivin ASODN mediated by cytofectin was directly injected into xenograft in 5 places. The volumes and weight of tumor mass were detected, respectively, and then tumor growth inhibitory rate and tumor growth index were calculated. Reverse transcription-polymerase chain reaction (RT-PCR) and immunochemohistology assay were performed to detect the expression level of survivin mRNA and protein.

RESULTS: In mice treated with single ASODN, the tumor growth inhibitory rate and tumor growth index was 35.4% and 4.23+/-0.4456. The difference of the tumor growth inhibitory rate and tumor growth index between blank control group and ASODN group was significant (P<0.05). While combined ASODN with cisplatin,the anticancer efficacy was far more significant and the tumor growth inhibitory rate was enhanced to 63.7%. The tumor growth index, however, reduced to 1.700+/-0.436, which was obviously significant,compared with the cisplatin group and other controls (P<0.05). The anticancer efficacy was even more obvious than that of ASODN group (P<0.05). Significant down-regulation of survivin mRNA and protein level expression in tumor tissues of ASODN group and ASODN and cisplatin group was detected by RT-PCR and immunochemohistology assay, respectively (P<0.05).

CONCLUSION: Survivin ASODN mediated by cytofectin can inhibit the cisplatin resistant tumor growth by direct intra-tumoral injection. The anticancer efficacy may be associated with the down regulation of survivin expression. ASODN targeting survivin gene can be a supportive therapy to cisplatin resistant lung cancer, while the clinical effective values need further exploration.