Delivery of a Survivin Promoter-driven Antisense Survivin-expressing Plasmid DNA As a Cancer Therapeutic: a Proof-of-concept Study

Overview

Journal Onco Targets Ther

Publisher Dove Medical Press

Specialty Oncology

Date 2016 May 25

PMID 27217778

Citations 7

Authors

Kun-Yuan Lin

Siao Muk Cheng

Shing-Ling Tsai

Ju-Ya Tsai

Chun-Hui Lin

Chun Hei Antonio Cheung

Affiliations

Soon will be listed here.

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.

Citing Articles

Apoptotic proteins with non-apoptotic activity: expression and function in cancer.

Shoshan-Barmatz V, Arif T, Shteinfer-Kuzmine A Apoptosis. 2023; 28(5-6):730-753.

PMID: 37014578 PMC: 10071271. DOI: 10.1007/s10495-023-01835-3.

Development of a cancer cells self‑activating and miR‑125a‑5p expressing poly‑pharmacological nanodrug for cancer treatment.

Chang Y, Shieh M, Chang Y, Huang W, Su W, Cheng F Int J Mol Med. 2022; 50(2).

PMID: 35703361 PMC: 9239037. DOI: 10.3892/ijmm.2022.5158.

Biodegradable mesoporous manganese carbonate nanocomposites for LED light-driven cancer therapy via enhancing photodynamic therapy and attenuating survivin expression.

Li L, Chen L, Huang L, Ye X, Lin Z, Wei X J Nanobiotechnology. 2021; 19(1):310.

PMID: 34627276 PMC: 8502371. DOI: 10.1186/s12951-021-01057-2.

Anti-apoptotic proteins in the autophagic world: an update on functions of XIAP, Survivin, and BRUCE.

Cheung C, Chang Y, Lin T, Cheng S, Leung E J Biomed Sci. 2020; 27(1):31.

PMID: 32019552 PMC: 7001279. DOI: 10.1186/s12929-020-0627-5.

Improved radioiodine-131 imaging of prostatic carcinoma using the sodium iodide symporter gene under control of the survivin promoter.

Zhao Z, Huang R, Cai H, Liu B, Zeng Y, Kuang A Int J Clin Exp Pathol. 2020; 11(8):4067-4072.

PMID: 31949797 PMC: 6962784.

References

Pei H, Li L, Fridley B, Jenkins G, Kalari K, Lingle W . FKBP51 affects cancer cell response to chemotherapy by negatively regulating Akt. Cancer Cell. 2009; 16(3):259-66. PMC: 2755578. DOI: 10.1016/j.ccr.2009.07.016. View

Olie R, Simoes-Wust A, Baumann B, Leech S, Fabbro D, Stahel R . A novel antisense oligonucleotide targeting survivin expression induces apoptosis and sensitizes lung cancer cells to chemotherapy. Cancer Res. 2000; 60(11):2805-9. View

Hsieh C, Kuo Y, Kuo C, Chen L, Cheung C, Chao T . Chamaecypanone C, a novel skeleton microtubule inhibitor, with anticancer activity by trigger caspase 8-Fas/FasL dependent apoptotic pathway in human cancer cells. Biochem Pharmacol. 2009; 79(9):1261-71. DOI: 10.1016/j.bcp.2009.12.017. View

Vequaud E, Seveno C, Loussouarn D, Engelhart L, Campone M, Juin P . YM155 potently triggers cell death in breast cancer cells through an autophagy-NF-kB network. Oncotarget. 2015; 6(15):13476-86. PMC: 4537028. DOI: 10.18632/oncotarget.3638. View

Mahboubi K, Li F, Plescia J, Kirkiles-Smith N, Mesri M, Du Y . Interleukin-11 up-regulates survivin expression in endothelial cells through a signal transducer and activator of transcription-3 pathway. Lab Invest. 2001; 81(3):327-34. DOI: 10.1038/labinvest.3780241. View

Li Y, Ma X, Wu X, Liu X, Liu L . Prognostic significance of survivin in breast cancer: meta-analysis. Breast J. 2014; 20(5):514-24. DOI: 10.1111/tbj.12303. View

Zhang H, Wang Y, Gao P, Lin F, Liu L, Yu B . Silencing stathmin gene expression by survivin promoter-driven siRNA vector to reverse malignant phenotype of tumor cells. Cancer Biol Ther. 2006; 5(11):1457-61. DOI: 10.4161/cbt.5.11.3272. View

Yie S, Lou B, Ye S, He X, Cao M, Xie K . Clinical significance of detecting survivin-expressing circulating cancer cells in patients with non-small cell lung cancer. Lung Cancer. 2008; 63(2):284-90. DOI: 10.1016/j.lungcan.2008.05.024. View

Sarela A, Macadam R, Farmery S, Markham A, Guillou P . Expression of the antiapoptosis gene, survivin, predicts death from recurrent colorectal carcinoma. Gut. 2000; 46(5):645-50. PMC: 1727921. DOI: 10.1136/gut.46.5.645. View

10.

Leung E, Kannan N, Krissansen G, Findlay M, Baguley B . MCF-7 breast cancer cells selected for tamoxifen resistance acquire new phenotypes differing in DNA content, phospho-HER2 and PAX2 expression, and rapamycin sensitivity. Cancer Biol Ther. 2010; 9(9):717-24. DOI: 10.4161/cbt.9.9.11432. View

11.

Goossens-Beumer I, Zeestraten E, Benard A, Christen T, Reimers M, Keijzer R . Clinical prognostic value of combined analysis of Aldh1, Survivin, and EpCAM expression in colorectal cancer. Br J Cancer. 2014; 110(12):2935-44. PMC: 4056050. DOI: 10.1038/bjc.2014.226. View

12.

Chen J, Li T, Liu Q, Jiao H, Yang W, Liu X . Clinical and prognostic significance of HIF-1α, PTEN, CD44v6, and survivin for gastric cancer: a meta-analysis. PLoS One. 2014; 9(3):e91842. PMC: 3960154. DOI: 10.1371/journal.pone.0091842. View

13.

Kuo C, Hsieh H, Pan W, Chen C, Liou J, Lee S . BPR0L075, a novel synthetic indole compound with antimitotic activity in human cancer cells, exerts effective antitumoral activity in vivo. Cancer Res. 2004; 64(13):4621-8. DOI: 10.1158/0008-5472.CAN-03-3474. View

14.

Liu C, Sun B, An N, Tan W, Cao L, Luo X . Inhibitory effect of Survivin promoter-regulated oncolytic adenovirus carrying P53 gene against gallbladder cancer. Mol Oncol. 2011; 5(6):545-54. PMC: 5528319. DOI: 10.1016/j.molonc.2011.10.001. View

15.

Wang R, Lin F, Wang X, Gao P, Dong K, Wei S . The therapeutic potential of survivin promoter-driven siRNA on suppressing tumor growth and enhancing radiosensitivity of human cervical carcinoma cells via downregulating hTERT gene expression. Cancer Biol Ther. 2007; 6(8):1295-301. DOI: 10.4161/cbt.6.8.4505. View

16.

Ryan B, Konecny G, Kahlert S, Wang H, Untch M, Meng G . Survivin expression in breast cancer predicts clinical outcome and is associated with HER2, VEGF, urokinase plasminogen activator and PAI-1. Ann Oncol. 2006; 17(4):597-604. DOI: 10.1093/annonc/mdj121. View

17.

Leung E, Kim J, Askarian-Amiri M, Joseph W, McKeage M, Baguley B . Hormone Resistance in Two MCF-7 Breast Cancer Cell Lines is Associated with Reduced mTOR Signaling, Decreased Glycolysis, and Increased Sensitivity to Cytotoxic Drugs. Front Oncol. 2014; 4:221. PMC: 4153047. DOI: 10.3389/fonc.2014.00221. View

18.

Cao M, Yie S, Wu S, Chen S, Lou B, He X . Detection of survivin-expressing circulating cancer cells in the peripheral blood of patients with esophageal squamous cell carcinoma and its clinical significance. Clin Exp Metastasis. 2009; 26(7):751-8. DOI: 10.1007/s10585-009-9274-7. View

19.

Hansen J, Fisker N, Westergaard M, Kjaerulff L, Hansen H, Thrue C . SPC3042: a proapoptotic survivin inhibitor. Mol Cancer Ther. 2008; 7(9):2736-45. DOI: 10.1158/1535-7163.MCT-08-0161. View

20.

Carrasco R, Stamm N, Marcusson E, Sandusky G, Iversen P, Patel B . Antisense inhibition of survivin expression as a cancer therapeutic. Mol Cancer Ther. 2011; 10(2):221-32. DOI: 10.1158/1535-7163.MCT-10-0756. View