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Treatment of liver cancer in mice by the intratumoral injection of an octreotide-based temperaturesensitive gel

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Octreotide (OCT) can inhibit tumor growth with few sideeffects. In this study, we hypothesized that an OCT- and poloxamer 407 (P407)-based temperaturesensitive gel may compensate for the short halflife of OCT, which may thus lead to the development of a novel therapy for patients with endstage liver cancer by intratumoral injection. The proliferation and apoptosis of mouse HcaF hepatocellular carcinoma cells were determined by MTT assay and Annexin VPI staining. A mouse model of hepatocellular carcinoma was established by the subcutaneous transplantion of HcaF cells and OCTP407 or OCT solution were injected into the tumors, followed by the detection of OCT levels by high performance liquid chromatography (HPLC) over a specific time period. OCTP407, ethanol, OCT, P407 or normal saline (NS) were injected into the tumors and the tumor size, weight and inhibition rate were measured 8 days later. Additionally, the expression of somatostatin receptor2 (SSTR2), vascular endothelial growth factor (VEGF) and caspase3 was detected by immunohistochemistry and RTPCR. Compared with the OCT group, the tumor inhibition rate and the apoptotic rate in the OCTP407 group were higher and the effects were longer. The tumor size and weight in the OCTP407 group were lower and the tumor inhibition rate higher compared with the OCT, P407 and NS groups, with the exception of the ethanol group. The protein and mRNA expression of SSTR2 and caspase3 in the OCTP407 group was higher, and that of VEFG was lower compared with the other groups, with the exception of the ethanol group. In the present study, we demonstrate that the intratumoral injection of OCTP407 maintains OCT local effective concentration and prolongs its action time, with a greater therapeutic effect than that of OCT on its own. Although ethanol is more effective in certain aspects, its tumor inhibitory effects are similar to OCTP407 and as such, OCTP407 may be a suitable alternative.
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Document Type: Research Article

Affiliations: 1: Department of Gastroenterology, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 2: Department of Clinical Pharmacy, College of Pharmacy, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 3: Morphology Laboratory, College of Basic of Medical Sciences, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 4: Department of Ultrasound, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 5: Department of Clinical Laboratory, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 6: Department of Digestive Endoscopy, The First Affiliated Hospital, Dalian Medical University, Dalian, Liaoning 116011, P.R. China 7: Dalian Medical University School of Public Health Research Statistics, Dalian, Liaoning 116011, P.R. China 8: Institute of Chemical Engineering, Dalian University of Technology, Dalian, Liaoning 116024, P.R. China 9: Department of Anesthesiology, Dalian Medical University, Dalian, Liaoning 116011, P.R. China

Publication date: January 1, 2014

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  • The International Journal of Molecular Medicine is a monthly, peer-reviewed journal devoted to the publication of high quality studies related to the molecular mechanisms of human disease. The journal welcomes research on all aspects of molecular and clinical research, ranging from biochemistry to immunology, pathology, genetics, human genomics, microbiology, molecular pathogenesis, molecular cardiology, molecular surgery and molecular psychology.

    The International Journal of Molecular Medicine aims to provide an insight for researchers within the community in regard to developing molecular tools and identifying molecular targets for the diagnosis and treatment of a diverse number of human diseases.
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