PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse

<p>Abstract</p> <p>Background</p> <p>Advanced ovarian cancer is characterized by peritoneal metastasis and the accumulation of ascites. Peritoneal metastasis of ovarian cancer is a major cause of the negative treatment outcome, as these metastases are resistant to most...

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Main Authors: Konishi Hiroaki, Takagi Akimitsu, Kurita Akinobu, Kaneda Norimasa, Matsuzaki Takeshi
Format: Article
Language:English
Published: BMC 2012-10-01
Series:BMC Cancer
Subjects:
Online Access:http://www.biomedcentral.com/1471-2407/12/462
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author Konishi Hiroaki
Takagi Akimitsu
Kurita Akinobu
Kaneda Norimasa
Matsuzaki Takeshi
author_facet Konishi Hiroaki
Takagi Akimitsu
Kurita Akinobu
Kaneda Norimasa
Matsuzaki Takeshi
author_sort Konishi Hiroaki
collection DOAJ
description <p>Abstract</p> <p>Background</p> <p>Advanced ovarian cancer is characterized by peritoneal metastasis and the accumulation of ascites. Peritoneal metastasis of ovarian cancer is a major cause of the negative treatment outcome, as these metastases are resistant to most chemotherapy regimens. The aim of this study was to clarify aggressive pathology of peritoneal metastasis and examine the therapeutic efficacy of a liposomal agent in the model.</p> <p>Methods</p> <p>A human cancer cell line ES-2 of ovarian clear cell carcinoma, known as a chemotherapy-resistant cancer, was cultured in nonadherent plate to form spheroid and single cell suspension was transplanted into mouse peritoneal cavity. The epidermal growth factor receptor (EGFR) pathways in the cellular aggregates were analyzed both spheroid and ascites. The pharmacokinetics and therapeutic efficacy of CPT-11 (45 mg/kg) and IHL-305 (45 mg/kg), an irinotecan-encapsulated liposome, were examined by intravenous administration.</p> <p>Results</p> <p>Established peritoneal metastasis model showed an accumulation of ascites. The activation of EGFR and Akt was demonstrated in cellular aggregates both in the spheroid and ascites. In ascites samples, the area under the curve of SN-38, the activated form of CPT-11, was 3.8 times higher from IHL-305-treated mice than from CPT-11-treated mice. IHL-305 prolonged the survival time and decreased the accumulation of ascites and tumor metastasis. The median survival time were 22, 37 and 54 days in the control, CPT-11-treated, and IHL-305-treated mice, respectively.</p> <p>Conclusions</p> <p>EGFR/Akt pathway contributes to the aggressive progression in ES-2 peritoneal metastasis model and effective delivery into ascites of IHL-305 was thought to useful treatment for ovarian cancer with peritoneal metastasis.</p>
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spelling doaj.art-5a8ef2d639b44a1391af780a9299b94b2022-12-22T00:36:17ZengBMCBMC Cancer1471-24072012-10-0112146210.1186/1471-2407-12-462PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouseKonishi HiroakiTakagi AkimitsuKurita AkinobuKaneda NorimasaMatsuzaki Takeshi<p>Abstract</p> <p>Background</p> <p>Advanced ovarian cancer is characterized by peritoneal metastasis and the accumulation of ascites. Peritoneal metastasis of ovarian cancer is a major cause of the negative treatment outcome, as these metastases are resistant to most chemotherapy regimens. The aim of this study was to clarify aggressive pathology of peritoneal metastasis and examine the therapeutic efficacy of a liposomal agent in the model.</p> <p>Methods</p> <p>A human cancer cell line ES-2 of ovarian clear cell carcinoma, known as a chemotherapy-resistant cancer, was cultured in nonadherent plate to form spheroid and single cell suspension was transplanted into mouse peritoneal cavity. The epidermal growth factor receptor (EGFR) pathways in the cellular aggregates were analyzed both spheroid and ascites. The pharmacokinetics and therapeutic efficacy of CPT-11 (45 mg/kg) and IHL-305 (45 mg/kg), an irinotecan-encapsulated liposome, were examined by intravenous administration.</p> <p>Results</p> <p>Established peritoneal metastasis model showed an accumulation of ascites. The activation of EGFR and Akt was demonstrated in cellular aggregates both in the spheroid and ascites. In ascites samples, the area under the curve of SN-38, the activated form of CPT-11, was 3.8 times higher from IHL-305-treated mice than from CPT-11-treated mice. IHL-305 prolonged the survival time and decreased the accumulation of ascites and tumor metastasis. The median survival time were 22, 37 and 54 days in the control, CPT-11-treated, and IHL-305-treated mice, respectively.</p> <p>Conclusions</p> <p>EGFR/Akt pathway contributes to the aggressive progression in ES-2 peritoneal metastasis model and effective delivery into ascites of IHL-305 was thought to useful treatment for ovarian cancer with peritoneal metastasis.</p>http://www.biomedcentral.com/1471-2407/12/462Ovarian cancerPeritoneal metastasisAscites fluidSpheroid cultureDrug delivery system
spellingShingle Konishi Hiroaki
Takagi Akimitsu
Kurita Akinobu
Kaneda Norimasa
Matsuzaki Takeshi
PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
BMC Cancer
Ovarian cancer
Peritoneal metastasis
Ascites fluid
Spheroid culture
Drug delivery system
title PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
title_full PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
title_fullStr PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
title_full_unstemmed PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
title_short PEGylated liposome IHL-305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
title_sort pegylated liposome ihl 305 markedly improved the survival of ovarian cancer peritoneal metastasis in mouse
topic Ovarian cancer
Peritoneal metastasis
Ascites fluid
Spheroid culture
Drug delivery system
url http://www.biomedcentral.com/1471-2407/12/462
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AT kuritaakinobu pegylatedliposomeihl305markedlyimprovedthesurvivalofovariancancerperitonealmetastasisinmouse
AT kanedanorimasa pegylatedliposomeihl305markedlyimprovedthesurvivalofovariancancerperitonealmetastasisinmouse
AT matsuzakitakeshi pegylatedliposomeihl305markedlyimprovedthesurvivalofovariancancerperitonealmetastasisinmouse