Abstract
To investigate the antitumor activity and mechanism of chloroquine (CQ) in combination with cisplatin (DDP) in nude mice xenografted with gastric cancer SGC7901 cells. 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. 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). Antitumor ability of cisplatin was associated with autophagy activity and chloroquine can enhance chemosensitivity to cisplatin in gastric cancer xenografts nude mice.
Highlights
Gastric cancer is the fourth most common malignancy and the second leading cause of cancer deaths worldwide
Rapid tumor growth was noticed in control group (Con) group, the growth was relatively slow in difference (P>0.05). Compared with cisplatin (DDP) group and CQ+DDP group
In the process of observation, compared with Con group, the xenograft tumor volume was smaller in CQ group (P
Summary
Gastric cancer is the fourth most common malignancy and the second leading cause of cancer deaths worldwide. A total of 989,600 new stomach cancer cases and 738,000 deaths are estimated to have occurred in 2008, accounting for 8% of the total cases and 10% of total deaths. Over 70% of new cases and deaths occur in developing countries, with the majority in China (Jemal et al, 2011). Resistance to chemotherapy is a major impediment of successful systemic treatment of gastric cancer. Autophagy is often regarded as the survival and protective mechanism under stress conditions in the body. It can maintain the integrity of the cell by regenerating metabolic precursors and removing subcellular fragments
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