Systemic administration of antisense oligonucleotides simultaneously targeting CK2α and α′ subunits reduces orthotopic xenograft prostate tumors in mice

  • Janeen H. Trembley
  • Gretchen M. Unger
  • Diane K. Tobolt
  • Vicci L. Korman
  • Guixia Wang
  • Kashif A. Ahmad
  • Joel W. Slaton
  • Betsy T. Kren
  • Khalil AhmedEmail author


CK2 is a highly conserved, ubiquitous, signal responsive protein serine/threonine kinase. CK2 promotes cell proliferation and suppresses apoptosis, and increased CK2 expression is observed in all cancers examined. We previously reported that direct injection of antisense (AS) CK2α phosphorothioate oligonucleotides (PTO) into xenograft prostate tumors in mice significantly reduced tumor size. Downregulation of CK2α in tumor cells in vivo appeared to result in overexpression of CK2α′ protein. This suggested that in cancer cells downregulation of CK2α might be compensated by CK2α′ in vivo, prompting us to design a bispecific (bs) AS PTO (bs-AS-CK2) targeting both catalytic subunits. bs-AS-CK2 reduced CK2α and α′ protein expression, decreased cell proliferation, and induced apoptosis in cultured cells. Biodistribution studies of administered bs-AS-CK2 oligonucleotide demonstrated its presence in orthotopic prostate xenograft tumors. High dose injections of bs-AS-CK2 resulted in no damage to normal liver or prostate, but induced extensive cell death in tumor tissue. Intraperitoneal treatment with bs-AS-CK2 PTO decreased orthotopic tumor size and downregulated both CK2 mRNA and protein expression. Tumor reduction was accomplished using remarkably low doses and was improved by dividing the dose using a multi-day schedule. Decreased expression of the key signaling pathway proteins NF-κB p65 and AKT was also observed. We propose that the molecular downregulation of CK2 through bispecific targeting of the two catalytic subunits may be uniquely useful for therapeutic elimination of tumors.


CK2 Prostate cancer Antisense NF-κB AKT Biodistribution 







Official acronym for former casein kinase 2 or II


Castration-resistant prostate cancer




Glyceraldehyde 3-phosphate dehydrogenase


Hematoxylin and eosin stain




Head and neck squamous cell carcinoma






Kilo Dalton


Lactate dehydrogenase




Nuclear factor kappa B




Phosphate-buffered saline


Prostate cancer


Polymerase chain reaction


Protein kinase B


Phosphorothioate-modified oligodeoxynucleotide


Red fluorescent protein







The authors thank Ms. Lindsey M. Watch for excellent technical assistance. Grant Sponsors: Department of Veterans Affairs Medical Research Merit Review Funds (KA); National Cancer Institute grant numbers UO1-CA15062 (KA) and RO1-CA150182 (KA); National Institute of Health grant number R01-DK067436 (BK).

Conflict of interest



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Copyright information

© Springer Science+Business Media, LLC. (outside the USA) 2011

Authors and Affiliations

  • Janeen H. Trembley
    • 1
    • 2
  • Gretchen M. Unger
    • 6
  • Diane K. Tobolt
    • 6
  • Vicci L. Korman
    • 6
  • Guixia Wang
    • 1
    • 2
    • 8
  • Kashif A. Ahmad
    • 1
    • 2
    • 9
  • Joel W. Slaton
    • 3
  • Betsy T. Kren
    • 1
    • 4
  • Khalil Ahmed
    • 1
    • 2
    • 3
    • 5
    • 7
    Email author
  1. 1.Research Service, Minneapolis VA Health Care SystemUniversity of MinnesotaMinneapolisUSA
  2. 2.Department of Laboratory Medicine and PathologyUniversity of MinnesotaMinneapolisUSA
  3. 3.Department of UrologyUniversity of MinnesotaMinneapolisUSA
  4. 4.Department of MedicineUniversity of MinnesotaMinneapolisUSA
  5. 5.Masonic Cancer CenterUniversity of MinnesotaMinneapolisUSA
  6. 6.GeneSegues Inc.MinneapolisUSA
  7. 7.Cellular and Molecular Biochemistry Research Laboratory (151)Minneapolis VA Health Care System, University of MinnesotaMinneapolisUSA
  8. 8.The First Hospital of Jilin UniversityJilinChina
  9. 9.Northwestern Health Sciences UniversityBloomingtonUSA

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