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

ZHANG Mei-chun~ 1,2,* , HU Cheng-ping~ 1 , CHEN Qiong~ 1 , XIA Ying~ 3 (1.Department of Respiratory Medicine of Xiangya Hospital,Central South University, Changsha 410008; 2.Department of Respiratory Medicine,First Municiple People’s Hospital,Guangzhou Medical College,Guangzhou 510180; 3. Third Department of Thoracic Medicine,Central Hospital,Changsha 410004, China)  

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 (P0.05).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 (P0.05). The anticancer efficacy was even more obvious than that of ASODN group (P0.05). 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 (P0.05). 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.

【Key Words】： lung cancer survivin gene gene therapy antisense oligodeoxynucleotide multi-drug resistance
【CateGory Index】： R734.2

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