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Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient
Authors:Tomomi Aga  Kazuhira Endo  Akira Tsuji  Mitsuharu Aga  Makiko Moriyama-Kita  Takayoshi Ueno  Yosuke Nakanishi  Miyako Hatano  Satoru Kondo  Hisashi Sugimoto  Naohiro Wakisaka  Tomokazu Yoshizaki
Affiliation:1. Division of Otolaryngology — Head and Neck Surgery, Graduate School of Medicine, Kanazawa University, Kanazawa, Japan;2. Division of Otolaryngology, Toyama City Hospital, Toyama, Japan
Abstract:

Objectives

A combination of platinum-based chemotherapy and radiotherapy is the standard treatment for nasopharyngeal carcinoma (NPC). However, the efficacy of chemotherapy has reached a plateau. Many autophagy studies suggest that autophagy can either promote or suppress to cancer progression. Thus, a role of autophagy in the acquisition of chemoradioresistance has recently been a notable event. Therefore, we examined the relationship between autophagy and chemotherapy in NPC.

Methods

The expression of Beclin 1 and microtubule-associated protein light chain 3 (LC3), a marker of autophagy, was determined by immunohistochemistry in the biopsy samples of patients with NPC before and after the first course of chemotherapy. Additionally, to investigate in the effect of autophagy suppression in chemotherapy, NPC cell line C666-1 cells were treated with cisplatin and/or chloroquine, an inhibitor of autophagy.

Results

The expression of Beclin 1 increased after chemotherapy in all patients. In NPC cell line C666-1, compared to cisplatin alone, combination therapy (cisplatin and chloroquine) reduced cell viability, and promoted cell apoptosis.

Conclusions

These results suggest that autophagy, represented by Beclin 1, is upregulated after chemotherapy in both in vitro and in vivo NPC studies. Inhibition of autophagy could therefore be new strategy for NPC treatment.
Keywords:Autophagy  Beclin 1  Chloroquine  LC3  Nasopharyngeal carcinoma
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