Int. J. Mol. Sci. 2013, 14(6), 11942-11962; doi:10.3390/ijms140611942
Article

Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo

1 Division of Experimental Urology, Innsbruck Medical University, 6020 Innsbruck, Anichstraße 35, Austria 2 Department of Internal Medicine IV—Nephrology and Hypertension, Innsbruck Medical University, 6020 Innsbruck, Anichstraße 35, Austria 3 Oncotyrol Center for Personalized Cancer Medicine GmbH, Karl-Kapferer-Straße 5, 6020 Innsbruck, Austria 4 Karlsruhe Institute of Technology, Institute of Toxicology and Genetics, Toxicology and Genetics, Hermann-von-Helmholtz-Platz 1, 76344 Eggenstein-Leopoldshafen, Germany
* Author to whom correspondence should be addressed.
Received: 18 April 2013; in revised form: 29 May 2013 / Accepted: 29 May 2013 / Published: 4 June 2013
(This article belongs to the Special Issue Molecular Research in Urology)
PDF Full-text Download PDF Full-Text [899 KB, uploaded 4 June 2013 14:42 CEST]
Abstract: Progression to castration resistance is a major problem in the treatment of advanced prostate cancer and is likely to be driven by activation of several molecular pathways, including androgen receptor (AR) and cyclic AMP-dependent protein kinase A (PKA). In this study, we examined the therapeutic efficacy of a combined inhibition of the AR and the regulatory subunit type Iα (RIα) of protein kinase A with second generation antisense oligonucleotides (ODNs) in androgen-sensitive LNCaP and castration-resistant LNCaPabl tumors in vivo. We found that targeting the AR alone inhibited LNCaP, as well as LNCaPabl tumors. Combined inhibition resulted in an improved response over single targeting and even a complete tumor remission in LNCaPabl. Western blot analysis revealed that both ODNs were effective in reducing their target proteins when administered alone or in combination. In addition, treatment with the ODNs was associated with an induction of apoptosis. Our data suggest that dual targeting of the AR and PKARIα is more effective in inhibiting LNCaP and LNCaPabl tumor growth than single treatment and may give a treatment benefit, especially in castration-resistant prostate cancers.
Keywords: androgen receptor; cAMP-dependent protein kinase A; regulatory subunit type Iα; prostate cancer; antisense molecules; dual targeting; LNCaP xenografts; castration resistance

Article Statistics

Load and display the download statistics.

Citations to this Article

Cite This Article

MDPI and ACS Style

Eder, I.E.; Egger, M.; Neuwirt, H.; Seifarth, C.; Maddalo, D.; Desiniotis, A.; Schäfer, G.; Puhr, M.; Bektic, J.; Cato, A.C.B.; Klocker, H. Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo. Int. J. Mol. Sci. 2013, 14, 11942-11962.

AMA Style

Eder IE, Egger M, Neuwirt H, Seifarth C, Maddalo D, Desiniotis A, Schäfer G, Puhr M, Bektic J, Cato ACB, Klocker H. Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo. International Journal of Molecular Sciences. 2013; 14(6):11942-11962.

Chicago/Turabian Style

Eder, Iris E.; Egger, Martina; Neuwirt, Hannes; Seifarth, Christof; Maddalo, Danilo; Desiniotis, Andreas; Schäfer, Georg; Puhr, Martin; Bektic, Jasmin; Cato, Andrew C.B.; Klocker, Helmut. 2013. "Enhanced Inhibition of Prostate Tumor Growth by Dual Targeting the Androgen Receptor and the Regulatory Subunit Type Iα of Protein Kinase A in Vivo." Int. J. Mol. Sci. 14, no. 6: 11942-11962.

Int. J. Mol. Sci. EISSN 1422-0067 Published by MDPI AG, Basel, Switzerland RSS E-Mail Table of Contents Alert