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Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer
Authors:Keyang Qian  Hanqing Qian  Juan Cai  Wuheng Yue  Xiaoxiao Yu  Baorui Liu
Institution:1. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, China;2. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China;3. The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Traditional Chinese and Western Medicine, Nanjing University of Chinese Medicine, Nanjing, 210008, China;4. School of Basic Medicine and Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210000, China
Abstract:Gastric cancer, one of the most common disease, has become a major public health problem worldwide. Cisplatin (DDP) has been a widely used drug for the treatment of cancer, also usually applied in gastric cancer in clinic. However, the side effects including toxicity and drug-resistance restricted the usage of DDP in clinic, so we prepared a DDP-complexed hydrogel (DDP-Gel) and investigated its efficacy in gastric cancer. For in vivo studies, MKN45-Luc cells were injected into BLAB/C node mice subcutaneously to establish gastric cancer with orthotopically grown tumors. Mice bearing tumors were treated with normal saline, DDP and DDP-Gel. Body weight and survival condition were observed and recorded. The treatment efficacy in vivo was detected by luciferase imaging and histological evaluation was performed by H&E staining of different organs. Additionally, normal ICR mice were treated with different doses of DDP/DDP-Gel to calculate their LD50 in vivo. The results showed that DDP-Gel prolonged survival time and ameliorated body weight changes of mice bearing tumors. DDP-Gel exhibited higher efficacy to inhibit tumor growth and metastasis, compared to DDP. Besides, LD50 of DDP-Gel was 166.0?mg/kg, 13.2 folds higher than DDP. As a conclusion, DDP-Gel showed a more effective and safer function than DDP in gastric cancer, which indicating that DDP-Gel might be a novel strategy for gastric cancer therapy.
Keywords:Orthotopic  Gastric cancer  Cisplatin  Hydrogel  Toxicity
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