Abstract
Objective To explore antitumor effect and its mechanism analysis of Chloroquine combination with chemotherapy for esophageal cancer in situ transplantation. Methods 60 esophageal orthotopic transplantation tumor models were randomly divided into control group, 3-methyladenine (3-MA), paclitaxel and cisplatin combined therapy (TP) chemotherapy group and combination group. After 30 days treatment, tumor volume in four groups was analyzed. Autophagy substrate p62 and microtubule-associated protein 1 light chain 3 (LC3) were analyzed by Western blotting. VPS34 kinase activity was analyzed by kinase reaction. The apoptosis of tumor cells was determined by TdT-mediated dUTP nick end labeling (TUNEL) staining. The concentration of chemotherapeutic drugs in tumor cells of mice was analyzed by high performance liquid chromatography (HPLC) analysis. Results Compared with control group, tumor volume in TP chemotherapy group and combination group tumor growth significantly reduced (P=0.002). Compared with TP chemotherapy group, tumor growth in combination group of mice significantly reduced (P=0.010). Compared with the control group, p62 protein in tumor tissues in 3-MA and combination group significantly accumulated (P=0.000). Compared with control group, LC3-Ⅱ/β-actin ratio in 3-MA and combination group obviously decreased (P=0.000). Compared with the control group, VPS34 kinase activity in 3-MA and combination group obviously decreased (P=0.000). Compared with control group, tumor cell apoptosis levels in TP chemotherapy group and combination group significantly increased (P=0.000). Compared with TP chemotherapy group, the levels of tumor cell apoptosis in combination group significantly increased (P=0.000). Conclusion 3-MA can inhibit tumor cell autophagy, improve the utilization rate of drugs and enhance the anti-tumor effect. Key words: 3-Methyladenine; Paclitaxel and cisplatin combined therapy chemotherapy; Autophagy; Esophageal cancer; Drug resistance
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