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Antitumor Activity of Chloroquine in Combination with Cisplatin in Human Gastric Cancer Xenografts

  • Zhang, Hui-Qing (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Fang, Nian (Gastrointestinal Department of Internal Medicine, The Fourth Affiliated Hospital of Nanchang University) ;
  • Liu, Xiao-Mei (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Xiong, Shu-Ping (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Liao, Yu-Qian (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Jin, Wen-Jian (Department of Geriatric Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Song, Rong-Feng (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital) ;
  • Wan, Yi-Ye (The Third Department of Medical Oncology, Jiangxi Provincial Cancer Hospital)
  • Published : 2015.05.18

Abstract

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and Methods: 35 cases of gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection was performed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancer cells. In addition, 24 tumor-bearing mice were randomly divided into control, DDP, CQ and CQ + DDP groups. Results: In 54.3% (19/35) of patients the treatment was therapeutically effective (OR), 5 days after peritoneal chemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2 cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude mice in the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibition rate increased to 84.7% (P<0.01). The LC3-II/I ratio, and Beclin1 and MDR1/P-gp expression were decreased, while caspase 3 protein levels increased (P<0.05). Conclusions: Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.

Keywords

Cisplatin;chloroquine;gastric cancer;multi-drug resistance;xenografts

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