Inhibition of autophagy by chloroquine makes chemotherapy in nasopharyngeal carcinoma more efficient

• Published in: Auris, nasus, larynx nasus, larynx, 2019-06, Vol.46 (3), p.443-450
• Main Authors: Aga, Tomomi, Endo, Kazuhira, Tsuji, Akira, Aga, Mitsuharu, Moriyama-Kita, Makiko, Ueno, Takayoshi, Nakanishi, Yosuke, Hatano, Miyako, Kondo, Satoru, Sugimoto, Hisashi, Wakisaka, Naohiro, Yoshizaki, Tomokazu
• Format: Article
• Language: English
• Subjects: Adolescent; Adult; Aged; Antineoplastic Agents - pharmacology; Antineoplastic Agents - therapeutic use; Apoptosis - drug effects; Autophagy; Autophagy - drug effects; Beclin 1; Beclin-1 - metabolism; Cell Line, Tumor; Cell Survival - drug effects; Chemoradiotherapy; Chloroquine; Chloroquine - pharmacology; Cisplatin - pharmacology; Cisplatin - therapeutic use; Drug Resistance, Neoplasm; Female; Humans; LC3; Male; Microtubule-Associated Proteins - metabolism; Middle Aged; Nasopharyngeal carcinoma; Nasopharyngeal Carcinoma - metabolism; Nasopharyngeal Carcinoma - therapy; Nasopharyngeal Neoplasms - metabolism; Nasopharyngeal Neoplasms - therapy; Young Adult
• ISSN: 0385-8146; 1879-1476
• DOI: 10.1016/j.anl.2018.10.013

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. 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. 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. 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.