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 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.
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Xing-guo
XG
Zhao
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Rui-jie
RJ
Sun
Key Laboratory of Cardiovascular Remodeling and Function Research, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Xiao-yan
XY
Yang
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Da-yu
DY
Liu
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Da-peng
DP
Lei
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Tong
T
Jin
Department of Otolaryngology, Qilu Hospital, Shandong University, Jinan, Shandong Province, China.
Xin-liang
XL
Pan
D000818:Animals; D017209:Apoptosis / Q000187:drug effects* / Q000235:genetics; D045744:Cell Line, Tumor; D002738:Chloroquine / Q000819:agonists / Q000494:pharmacology*; D002945:Cisplatin / Q000819:agonists / Q000494:pharmacology*; D054313:Drug Agonism; D005260:Female; D006801:Humans; D007012:Hypopharyngeal Neoplasms / Q000188:drug therapy* / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D023041:Xenograft Model Antitumor Assays
D002738:Chloroquine; D002945:Cisplatin