Selection and antitumor activity of anti-Bcl-2 DNAzymes.
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.
Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China.
Xinhui
X
Yang
Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China; Key Laboratory of Molecular Radiation Oncology, Hunan Province, China.
Zhi
Z
Li
Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China; Key Laboratory of Molecular Radiation Oncology, Hunan Province, China.
Lu
L
Zhang
Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China; Key Laboratory of Molecular Radiation Oncology, Hunan Province, China.
Jiang
J
He
Center for Molecular Medicine, Xiangya Hospital, Collaborative Innovation Center for Cancer Medicine, Central South University, Changsha, 410078, China; Key Laboratory of Molecular Radiation Oncology, Hunan Province, China. Electronic address: lunquansun@csu.edu.cn.
Lun-Quan
LQ
Sun
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival; D021881:DNA, Catalytic / Q000494:pharmacology*; D005260:Female; D006801:Humans; D007700:Kinetics; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D009841:Oligonucleotides / Q000235:genetics; D017239:Paclitaxel / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000037:antagonists & inhibitors* / Q000378:metabolism
D000970:Antineoplastic Agents; D021881:DNA, Catalytic; D009841:Oligonucleotides; D019253:Proto-Oncogene Proteins c-bcl-2; D017239:Paclitaxel
Apoptosis; Bcl-2; Chemoresistance; DNAzyme