Chloroquine-enhanced efficacy of cisplatin in the treatment of hypopharyngeal carcinoma in xenograft mice

Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been repor...

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Bibliographic Details
Published in:PloS one 2015-04, Vol.10 (4), p.e0126147
Main Authors: Zhao, Xing-guo, Sun, Rui-jie, Yang, Xiao-yan, Liu, Da-yu, Lei, Da-peng, Jin, Tong, Pan, Xin-liang
Format: Article
Language:English
Subjects:
Analysis
Animals
Anticancer properties
Antitumor activity
Apoptosis
Apoptosis - drug effects
Apoptosis - genetics
Autophagy
Breast cancer
Cancer therapies
Cell death
Cell Line, Tumor
Chemotherapy
Chloroquine
Chloroquine - agonists
Chloroquine - pharmacology
Cisplatin
Cisplatin - agonists
Cisplatin - pharmacology
Colon
Complications and side effects
Dosage and administration
Drug Agonism
Drug dosages
Drug therapy
Effectiveness
Esophageal cancer
Female
Head
Head & neck cancer
Humans
Hypopharyngeal Neoplasms - drug therapy
Hypopharyngeal Neoplasms - genetics
Hypopharyngeal Neoplasms - metabolism
Hypopharyngeal Neoplasms - pathology
Immunoglobulins
Inhibition
Laboratory animals
Liver
Medical prognosis
Mice
Mice, Inbred BALB C
Mice, Nude
Neck
Otolaryngology
Pancreas
Pancreatic cancer
Phagocytosis
Pharyngeal cancer
Prostate
Proteins
Radiation therapy
Squamous cell carcinoma
Studies
Survival
Survival analysis
Throat cancer
Tumorigenesis
Tumors
Xenograft Model Antitumor Assays
Xenografts
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Summary:Hypopharyngeal squamous cell carcinoma (HSCC) has the worst prognosis among head and neck cancers. Cisplatin (DDP)-based chemotherapy is an important part of multimodal treatments. However, resistance to DDP severely impairs the effectiveness of chemotherapy for HSCC. Chloroquine (CQ) has been reported to enhance the effectiveness of chemotherapy and radiotherapy in liver, pancreas, breast, prostate and colon tumors, but it is unclear whether CQ could increase the efficacy of DDP for treating HSCC. We inoculated BALB/c nude mice with a subcutaneous injection of human hypopharyngeal FaDu cells to generate our animal model. Mice were randomly divided into 4 groups and treated with vehicle control, CQ (60 mg/kg/day), DDP (5 mg/kg/6 days), or a combination of DDP and CQ. Tumor growth and survival of the mice were monitored. We found that CQ inhibited autophagy and increased DDP-induced apoptosis in the xenograft mouse model. CQ enhanced the efficacy of DDP, resulting in decreased tumor growth and prolonged survival of the mice. To test whether blocking autophagy enhanced the efficacy of DDP, FaDu cells were infected with lentiviral shRNA to Beclin-1 and inoculated into the flanks of nude mice. Inhibition of autophagy markedly enhanced the DDP-induced antitumor effect. Our study suggests that the addition of CQ to DDP-based chemotherapy could be a potential therapeutic strategy for treating HSCC, and the inhibition of autophagy may contribute to chemotherapy sensitization in HSCC.
ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0126147