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评估顺铂水凝胶用于提高胃癌局部抗肿瘤疗效的研究。

Evaluation of cisplatin-hydrogel for improving localized antitumor efficacy in gastric cancer.

作者信息

Qian Keyang, Qian Hanqing, Cai Juan, Yue Wuheng, Yu Xiaoxiao, Liu Baorui

机构信息

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Clinical College of Nanjing Medical University, Nanjing, 210008, China.

The Comprehensive Cancer Centre of Nanjing Drum Tower Hospital, Medical School of Nanjing University & Clinical Cancer Institute of Nanjing University, Nanjing, 210008, China.

出版信息

Pathol Res Pract. 2019 Apr;215(4):755-760. doi: 10.1016/j.prp.2019.01.005. Epub 2019 Jan 7.

DOI:10.1016/j.prp.2019.01.005
PMID:30718098
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 LD 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, LD 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.

摘要

胃癌是最常见的疾病之一,已成为全球主要的公共卫生问题。顺铂(DDP)一直是一种广泛用于治疗癌症的药物,在临床上也常用于治疗胃癌。然而,包括毒性和耐药性在内的副作用限制了DDP在临床上的使用,因此我们制备了一种顺铂复合水凝胶(DDP-Gel)并研究了其在胃癌治疗中的疗效。在体内研究中,将MKN45-Luc细胞皮下注射到BLAB/C裸鼠体内,以建立原位生长肿瘤的胃癌模型。对荷瘤小鼠分别用生理盐水、DDP和DDP-Gel进行治疗。观察并记录小鼠的体重和生存状况。通过荧光素酶成像检测体内治疗效果,通过对不同器官进行苏木精-伊红(H&E)染色进行组织学评估。此外,对正常ICR小鼠用不同剂量的DDP/DDP-Gel进行治疗,以计算它们在体内的半数致死量(LD)。结果表明,DDP-Gel延长了荷瘤小鼠的生存时间,并改善了其体重变化。与DDP相比,DDP-Gel在抑制肿瘤生长和转移方面表现出更高的疗效。此外,DDP-Gel的LD为166.0 mg/kg,比DDP高13.2倍。综上所述,DDP-Gel在胃癌治疗中比DDP表现出更有效和更安全的作用,这表明DDP-Gel可能是一种治疗胃癌的新策略。

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