[Inhibitory effects of survivin antisense oligonucleotide on drug-resistant human ovarian cancer cell COC1/DDP]

Fei Ruan, Xian-Kuan Xie, Shao-Yang Liu
Ai Zheng, Aizheng, Chinese Journal of Cancer 2004, 23 (8): 896-9

BACKGROUND & OBJECTIVE: Recent studies have shown that survivin is an anti-apoptosis gene, which plays an important role in the carcinogenesis and drug resistance of ovarian cancer. This study was designed to explore the effects of liposome-survivin antisense oligonucleotide (Lip-ASODN) on the growth,apoptosis,and cell cycle distribution of drug-resistant human ovarian cancer cell line COC1/DDP.

METHODS: Survivin-ASODN were transfected into COC1/DDP cells mediated by lipofectin. The proliferation of COC1/DDP cells was assessed by cyto-dynamics and MTT assay. The mRNA expression of survivin was determined by reverse transcription- polymerase chain reaction (RT-PCR). The caspase-3 protein activity was measured by Western blot analysis. The apoptotic rate and cell cycle distribution were estimated by flow cytometry (FCM).

RESULTS: Compared with Lip-SODN and Lip alone groups, the proliferation of COC1/DDP cells after cultured with Lip-ASODN has been significantly inhibited, its inhibitory rate was (68.3+/-6.2)% after cultured for 72 hours (P< 0.05). The mRNA expression of survivin in Lip-ASODN group was significantly decreased, while the caspase-3 activity increased in a time-dependent manner as compared with Lip-SODN and Lip alone groups (P< 0.05). Cell cycle distribution significantly changed in Lip-ASODN group, many cells have been blocked in G0/G1 phase (79.21%), while G2/M phase (4.92%) and S phase (15.87%) decreased. The apoptotic rate of Lip-ASODN group reached 33.18%, which was much higher than those of Lip-SODN and Lip alone groups (P< 0.05).

CONCLUSION: Survivin ASODN can inhibit COC(1)/DDP cell proliferation, reduce the mRNA expression of survivin, and induce cell apoptosis.

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