[Antisense oligonucleotide against survivin induces apoptosis and enhances adriamycin sensitivity of SMMC-7721/ADM cells]

Abstract

Objective: To explore the effects of survivin-specific antisense oligonucleotide (ASODN) delivered via liposome on the growth and apoptosis of drug-resistant human hepatic cancer cell line SMMC-7721/ADM and the sensitivity of the cells to adriamycin (ADM).

Methods: SMMC-7721/ADM cells were divided into 6 groups and treated with liposome, ADM, sense oligonucleotide (SODN), SODN+ADM, 400 ng/ml ASODN, and 400 ng/ml ASODN+ADM group, respectively. MTT assay was used to calculate the relative survival rates of the cells, and the changes in cell apoptosis and cycle were detected with flow cytometry. RT-PCR and Western blotting were performed to detect the expressions of survivin mRNA and protein, respectively.

Results: The apoptotic rate of ASODN-treated cells was much higher than that of the control cells. survivin protein expression showed no significant variation between cells treated with liposome, ADM, SODN, and SODN+ADM (P>0.05), whereas compared with these 4 groups, cells treated with 400 ng/ml ASODN and 400 ng/ml ASODN+ADM had significantly lowered survivin mRNA expression (P<0.05), without significant differences between the latter two groups (P>0.05). SMMC-7721/ADM cells cultured in the presence of ASODN and adriamycin showed significant growth inhibition in comparison with ASODN group and ADM group.

Conclusion: survivin-specific ASODN can enhance the sensitivity of SMMC-7721/ADM cells to ADM by depressing survivin expression in the cells, thus improves the effect of ADM chemotherapy for liver cancer.