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Lin KY, Cheng SM, Tsai SL, et al. Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study. Onco Targets Ther. 2016;9:2601-13doi: 10.2147/OTT.S101209.
Lin, K. Y., Cheng, S. M., Tsai, S. L., Tsai, J. Y., Lin, C. H., & Cheung, C. H. (2016). Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study. OncoTargets and therapy, 92601-13. https://doi.org/10.2147/OTT.S101209
Lin, Kun-Yuan, et al. "Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study." OncoTargets and therapy vol. 9 (2016): 2601-13. doi: https://doi.org/10.2147/OTT.S101209
Lin KY, Cheng SM, Tsai SL, Tsai JY, Lin CH, Cheung CH. Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study. Onco Targets Ther. 2016 May 03;9:2601-13. doi: 10.2147/OTT.S101209. eCollection 2016. PMID: 27217778; PMCID: PMC4862386.
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Onco Targets Ther. 2016 May 03;9:2601-13. doi: 10.2147/OTT.S101209. eCollection 2016.

Delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA as a cancer therapeutic: a proof-of-concept study.

OncoTargets and therapy

Kun-Yuan Lin, Siao Muk Cheng, Shing-Ling Tsai, Ju-Ya Tsai, Chun-Hui Lin, Chun Hei Antonio Cheung

Affiliations

  1. Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
  2. Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.
  3. Department of Pharmacology, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC; Institute of Basic Medical Sciences, College of Medicine, National Cheng Kung University, Tainan, Taiwan, ROC.

PMID: 27217778 PMCID: PMC4862386 DOI: 10.2147/OTT.S101209

Abstract

Survivin is a member of the inhibitor-of-apoptosis proteins family. It is overexpressed in many different cancer types but not in the differentiated normal tissue. In addition, overexpression of survivin promotes cancer cell survival and induces chemotherapeutic drug resistance, making it an attractive target for new anticancer interventions. Despite survivin being a promising molecular target for anticancer treatment, it is widely accepted that survivin is only a "semi-druggable" target. Therefore, it is important to develop a new strategy to target survivin for anticancer treatment. In this study, we constructed a novel survivin promoter-driven full-length antisense survivin (pSur/AS-Sur) expression plasmid DNA. Promoter activity assay revealed that the activity of the survivin promoter of pSur/AS-Sur correlated with the endogenous expression of survivin at the transcriptional level in the transfected A549, MDA-MB-231, and PANC-1 cancer cells. Western blot analysis showed that liposomal delivery of pSur/AS-Sur successfully downregulated the expression of survivin in A549, MBA-MB-231, and PANC-1 cells in vitro. In addition, delivery of pSur/AS-Sur induced autophagy, caspase-dependent apoptosis, and caspase-independent apoptosis as indicated by the increased LC3B-II conversion, autophagosome formation, caspase-9/-3 and poly(ADP-ribose) polymerase-1 cleavage, and apoptosis-inducing factor nuclear translocation in A549, MBA-MB-231, and PANC-1 cells. Importantly, liposomal delivery of pSur/AS-Sur was also capable of decreasing the proliferation of the survivin/MDR1 coexpressing multidrug-resistant KB-TAX50 cancer cells and the estrogen receptor-positive tamoxifen-resistant MCF7-TamC3 cancer cells in vitro. In conclusion, the results of this study suggest that delivery of a survivin promoter-driven antisense survivin-expressing plasmid DNA is a promising way to target survivin and to treat survivin-expressing cancers in the future.

Keywords: antisense; apoptosis; autophagy; cancer; liposomal delivery; survivin

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