[Antisense oligonucleotide targeting survivin induces apoptosis of renal clear-cell carcinoma cells and enhances their sensitivity to epirubicin in vitro]

Xiao-kang Gao, Qing Li, He Wang, Bo Yang, Jian-lin Yuan, Guo-xing Shao, Fu-xia Kang
Zhonghua Zhong Liu za Zhi [Chinese Journal of Oncology] 2005, 27 (8): 468-70

OBJECTIVE: To investigate the effect of antisense oligonucleotide (ASODN) targeting survivin on the apoptosis and proliferation of renal cancer cell line 786-O and enhancement of its sensitivity to epirubicin.

METHODS: ASODN targeting survivin was designed and constructed. Cultured cells were divided into 6 groups: control group, liposome group, sense oligonucleotide (SODN) group, 600 nmol/L ASODN group, and 600 nmol/L ASODN combined with epirubicin group. After transfected for 24 h, cultured cells were harvested to carry on the next tests. Cell morphological changes were examined by transmission electron microscopy. Survivin protein was detected by immunohistochemical method. Apoptosis index (AI) and proliferation index (PI) were examined by flow cytometry.

RESULTS: Morphological abnormalities of cells were observed in ASODN transfected groups. Expression of survivin in ASODN groups were significantly decreased compared with that in the control group, liposomes group and SODN group. AI of ASODN groups was significantly higher than that in other groups. PI of ASODN groups was significantly lower than that in other groups. The PI of ASODN combined with epirubicin group was (35.7 +/- 1.67)%, but (9.3 +/- 0.34)% or (8.5 +/- 0.21)% in liposomes group or SODN group that had combined with epirubicin. The ASODN group achieved the strongest effects to enhance apoptosis in comparison with control group (P < 0.05), while SODN did not cause statistically significant change (P > 0.05).

CONCLUSION: The expression of survivin protein in the renal clear cell carcinoma cell line 786-O is downregulated by survivin ASODN. ASODN targeting survivin induces apoptosis and inhibits proliferation of 786-O cells. Inhibition of survivin enhances sensitivity of 786-O to epirubicin.

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