Experimental study of antisense oligodeoxynucleotide targeting survivin gene for cisplatin resistant human lung adeno-carcinoma xenograft in nude mice.
- Author:
Mei-chun ZHANG
1
;
Cheng-ping HU
;
Qiong CHEN
;
Ying XIA
Author Information
1. Department of Respiratory Medicine, Xiangya Hospital, Central South University, Changsha 410008, China. meichunzhang82@126.com
- Publication Type:Journal Article
- MeSH:
Adenocarcinoma;
pathology;
therapy;
Animals;
Cisplatin;
pharmacology;
Drug Resistance, Neoplasm;
Female;
Genetic Therapy;
Humans;
Inhibitor of Apoptosis Proteins;
Lung Neoplasms;
pathology;
therapy;
Male;
Mice;
Mice, Inbred BALB C;
Mice, Nude;
Microtubule-Associated Proteins;
genetics;
therapeutic use;
Neoplasm Transplantation;
Oligonucleotides, Antisense;
therapeutic use;
Repressor Proteins;
Survivin
- From:
Journal of Central South University(Medical Sciences)
2006;31(5):717-722
- CountryChina
- Language:Chinese
-
Abstract:
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.
