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Oncotarget. 2017 Nov 6;8(65):108848-108858. doi: 10.18632/oncotarget.22312. eCollection 2017 Dec 12.

Improvement of anti-cancer drug efficacy via thermosensitive hydrogel in peritoneal carcinomatosis in gastric cancer.

Author information

1
Cancer Research Institute, Seoul National University College of Medicine, Seoul, Korea.
2
Biotherapeutics Translational Research Center, Korea Research Institute of Bioscience and Biotechnology, Daejeon, Korea.
3
Department of Biochemistry and Cell Biology, Cell and Matrix Research Institute, School of Medicine, Kyungpook National University, Daegu, Korea.
4
Department of Pathology, Seoul National University College of Medicine, Seoul, Korea.
5
Center for Biomaterials, Korea Institute of Science and Technology, Seoul, Korea.
6
ezlab, Suwon, Korea.
7
Department of Surgery, Seoul National University College of Medicine, Seoul, Korea.
8
Division of Biomarker Discovery, Exploratory Oncology Research & Clinical Trial Center, National Cancer Center, Tokyo, Japan.

Abstract

Peritoneal carcinomatosis (PC) of gastric origin has a poor prognosis with short survival due to lack of effective therapeutic modalities. Here, we evaluated the therapeutic efficacy of an injectable thermosensitive poly (organophosphazene) (PPZ) hydrogel with docetaxel (DTX-gel) to develop an effective therapeutic agent for patient with PC. Three days after inoculation of highly metastatic 44As3Luc cells into peritoneal cavity, the mice were intravenously or intraperitoneally administered with docetaxel alone (DTX-sol IV or IP), and intraperitoneally injected with DTX-gel. The anti-tumor activity was monitored by bioluminescence live imaging system. Compared to DTX-sol IV or IP, the tumor growth was significantly reduced in the DTX-gel treated mice (p<0.0001, p=0.0001). Furthermore, the survival rate was significantly increased in the DTX-gel treated mice compared to DTX-sol IV or IP treated mice (p<0.0001, p=0.0068). Our results demonstrated that DTX-gel suppresses peritoneal metastasis by continuing release of chemotherapy agent, which leads to increase the survival rate in a PC model. Therefore, biodegradable thermosensitive hydrogel with docetaxel system can be a good anti-cancer agent for PC.

KEYWORDS:

PPZ hydrogel; docetaxel; gastric cancer; live imaging; peritoneal carcinomatosis

Conflict of interest statement

CONFLICTS OF INTEREST The authors disclose no conflicts.

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