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Ritonavir Exhibits Limited Efficacy as a Single Agent in Treating Aggressive Mantle Cell Lymphoma | OMICS International | Abstract
ISSN: 1948-5956

Journal of Cancer Science & Therapy
Open Access

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Research Article

Ritonavir Exhibits Limited Efficacy as a Single Agent in Treating Aggressive Mantle Cell Lymphoma

Tara M. Nordgren, Ganapati V. Hegde and Shantaram S. Joshi*

Department of Genetics, Cell Biology and Anatomy, University of Nebraska Medical Center. Omaha, NE 68198-6395, USA

*Corresponding Author:
Shantaram S. Joshi, PhD
Department of Genetics
Cell Biology and Anatomy
986395 University of Nebraska Medical Center
Omaha, NE 68198-6395, USA
Tel: (402) 559-4165
Fax: (402) 559-3400
E-mail: [email protected]

Received date: March 12, 2012; Accepted date: April 09, 2012; Published date: April 11, 2012

Citation: Nordgren TM, Hegde GV, Joshi SS (2012) Ritonavir Exhibits Limited Efficacy as a Single Agent in Treating Aggressive Mantle Cell Lymphoma. J Cancer Sci Ther 4: 061-068. doi:10.4172/1948-5956.1000037

Copyright: © 2012 Nordgren TM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Mantle Cell Lymphoma (MCL) is an aggressive B cell malignancy accounting for 6% of non- Hodgkin’s lymphoma cases in the US. While various therapies are available to treat MCL, patients relapse within 3 to 4 years following treatment from therapy-resistant MCL, making MCL carry one of the worst prognoses of all non- Hodgkin’s B cell lymphomas. A better understanding of the biological mechanisms of relapse and therapy-resistance in MCL is vital for developing mechanisms to target relapsing MCL, and providing better care for patients. Recent studies implicate the NFκB pathway and survivin in promotion of aggressive, therapy-resistant MCL. Therefore, we tested the efficacy of inhibiting this pathway in three MCL lines (GP, recently-developed GRL, and JVM2) using the protease inhibitor ritonavir (Abbott Laboratories), which has been shown to downregulate NFκB targets, including survivin, in other hematological malignancies.

Methods: MCL cells were incubated with ritonavir then assessed for changes in proliferation, apoptosis, and activation of NFκB transcriptional targets. In addition, in vivo studies were performed to assess ritonavir’s utility as a single agent in MCL treatment using an immune-deficient mouse model of human MCL.

Results: When MCL cell lines were incubated with ritonavir in vitro, they exhibited reduced proliferation, increased apoptosis, and downregulation of NFκB pathway targets. However, no effect was seen when testing ritonavir as a single agent in vivo. Although, treatment with ritonavir plus vincristine in vitro revealed significant reduction in the proliferation of MCL compared to either treatment alone.

Conclusions: These studies suggest ritonavir is not suitable as a single-agent therapy for MCL. However, studies combining ritonavir plus vincristine in vitro suggest ritonavir may be effective in multi-pronged treatment approaches for MCL. These findings necessitate further studies to determine ritonavir’s utility within a multi-pronged treatment approach for treating therapy-resistant MCL.

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