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Synergistic Effect of Immunoliposomal Gemcitabine and Bevacizumab in Glioblastoma Stem Cell-Targeted Therapy

Authors
Shin, Dae HwanLee, Sang-JinKim, Jung SeokRyu, Jae-HaKim, Jin-Seok
Issue Date
Oct-2015
Publisher
AMER SCIENTIFIC PUBLISHERS
Keywords
Glioblastoma Stem Cells; Targeting; Liposomes; Synergism; Bevacizumab; Gemcitabine
Citation
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY, v.11, no.11, pp 1989 - 2002
Pages
14
Journal Title
JOURNAL OF BIOMEDICAL NANOTECHNOLOGY
Volume
11
Number
11
Start Page
1989
End Page
2002
URI
https://scholarworks.sookmyung.ac.kr/handle/2020.sw.sookmyung/10175
DOI
10.1166/jbn.2015.2146
ISSN
1550-7033
1550-7041
Abstract
Glioblastoma stem cells have been shown to confer chemoresistance and radioresistance, leading to angiogenesis and the recurrence of tumors in glioblastoma multiforme. Combination therapy targeting glioblastoma stem cells and antiangiogenesis has been a focus of treatment strategies because of the enhanced efficacy achieved by dual inhibition of tumor proliferation and nutrient delivery. In this study, glioblastoma stem cells and glioblastoma stem cell-induced angiogenesis in glioblastoma multiforme were challenged by combined treatment with anti-CD133 monoclonal antibody conjugated liposomes encapsulating gemcitabine and bevacizumab. Both liposomal encapsulation and conjugation of an anti-CD133 antibody significantly enhanced the cytotoxicity of gemcitabine toward glioblastoma stem cells in vitro. Moreover, combined treatment with this gemcitabine formulation and bevacizumab significantly inhibited tube formation, migration, and proliferation of endothelial cells in vitro. The antitumor efficacy of immunoliposomal gemcitabine and bevacizumab combination therapy in a xenograft model was significantly greater than that of monotherapy, presumably reflecting the enhanced effects on glioblastoma stem cells themselves and glioblastoma stem cell-induced angiogenesis caused by synergistic interactions between the two drugs. Moreover, combination therapy prolonged the mean survival time of xenografted mice. Taken altogether, our results suggest that combined therapy with immunoliposomal gemcitabine and bevacizumab shows promise for the treatment of glioblastoma multiforme.
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