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Selection and antitumor activity of anti-Bcl-2 DNAzymes
Xinhui Yang1, Zhi Li2, Lu Zhang2
1Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China.
Abstract:
Apoptosis pathway has become one of the important targets for therapeutic exploration for cancer therapy. The increased Bcl-2 protein level and phosphorylation is implicated in a decreased chemotherapeutic response in many cancers. BCL-2 inhibitors have been developed as direct inducers of apoptosis. However, resistance to BCL2 inhibitors has been emerging and thus considerable effort has been made to seek novel approaches to BCL2 suppression. In this report we describe an in vitro DNAzyme selection strategy resulting in molecules that are effective in suppressing expression of the target gene BCL-2 in vitro. A 3'-inverted modification was shown to significantly increase the DNAzyme stability in serum and the modified DNAzyme delivered by an osmotic pump chemosensitized human prostate cancer to Taxol in vivo. Thus this study provides an alternative strategy for potential BCL-2-targetd therapy.
Insights
Researchers developed DNAzymes to suppress BCL-2 gene expression, offering a new strategy for cancer therapy. Modified DNAzymes enhanced prostate cancer chemosensitivity in vivo.
Area of Science:
- Molecular Biology
- Cancer Therapeutics
- Gene Regulation
Background:
- The apoptosis pathway is a key target in cancer therapy.
- Elevated BCL-2 protein levels correlate with reduced response to chemotherapy.
- Emerging resistance to BCL-2 inhibitors necessitates novel suppression strategies.
Purpose of the Study:
- To develop novel DNA molecules for BCL-2 gene suppression.
- To investigate the efficacy of DNAzymes in targeting BCL-2.
- To explore new therapeutic strategies for BCL-2-targeted cancer treatment.
Main Methods:
- In vitro DNAzyme selection strategy was employed.
- DNAzymes were designed to suppress BCL-2 gene expression.
- Modified DNAzymes with enhanced serum stability were tested in vivo.
Main Results:
- Selected DNAzymes effectively suppressed BCL-2 gene expression in vitro.
- A 3'-inverted modification significantly improved DNAzyme stability in serum.
- DNAzyme delivery via osmotic pump chemosensitized prostate cancer to Taxol in vivo.
Conclusions:
- DNAzymes represent a viable strategy for BCL-2 suppression.
- Modified DNAzymes show potential for enhancing cancer therapy efficacy.
- This approach offers an alternative to existing BCL-2-targeted therapies.
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