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

Purpose: To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination withcisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. Materials and
Methods: 35 casesof gastric cancer patients with malignant ascites were enrolled and intraperitoneal cisplatin injection wasperformed. Ascites were collected before and 5 days after perfusion for assessment of autophagy levels in cancercells. 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 peritonealchemotherapy, 13 patients had the decreased ascites Beclin-1 mRNA levels. In 16 patients who had NR, only 2cases had decreased Beclin-1 (P=0.001). Compared with the control group, the xenograft growth in nude micein the DDP group was low, and the inhibition rate was 47.6%. In combination with chloroquine, the inhibitionrate 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 withautophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nudemice.