title: The role of autophagy in the cytotoxicity induced by recombinant human arginase in laryngeal squamous cell carcinoma.
abstract: Laryngeal squamous cell carcinoma (LSCC), one of the most common malignant solid tumors in the world, has a high rate of mortality, recurrence, and metastasis. Recombinant human arginase (rhArg) recently has been developed in arginine deprivation therapy for a number of malignant tumors. In the present study, we observed that rhArg triggered significant cytotoxicity in human laryngeal squamous cell carcinoma Tu212 cells. Meanwhile, we observed that rhArg simultaneously activated autophagic flux in Tu212 cells, which was demonstrated by the accumulation of autophagosome and light chain 3 II (LC3-II). And, we explored the role of autophagy in cytotoxicity induced by rhArg in Tu212 cells. Autophagy inhibitors including chloroquine (CQ) and bafilomycin A1 (Baf A1) enhanced cytotoxicity induced by rhArg, implying the protective role of autophagy in rhArg-treated Tu212 cells. Moreover, Akt/mTOR signaling pathway was most possibly to participate in the rhArg-induced autophagy. Meanwhile, rhArg could upregulate the phosphorylation of ERK1/2 in a time-dependent manner. Therefore, all the results illuminated the cytoprotective role of autophagy in the treatment of rhArg in laryngeal squamous carcinoma Tu212 cells and provided a potential approach for LSCC therapy by rhArg combined with autophagy inhibitors.
authors.affiliation: Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Chen
authors.initials: C
authors.lastname: Lin
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.|Department of Biopharmaceutical Research, Shanghai Institute of Pharmaceutical Industry, Shanghai, China.
authors.forename: Ziyu
authors.initials: Z
authors.lastname: Wang
authors.affiliation: Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Li
authors.initials: L
authors.lastname: Li
authors.affiliation: Department of Otolaryngology, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang Province, China.
authors.forename: Yong
authors.initials: Y
authors.lastname: He
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China.
authors.forename: Jiajun
authors.initials: J
authors.lastname: Fan
authors.affiliation: Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China.
authors.forename: Zhongyu
authors.initials: Z
authors.lastname: Liu
authors.affiliation: Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, Shanghai, 200003, China. 13621671816@163.com.
authors.forename: Shuwei
authors.initials: S
authors.lastname: Zhao
authors.affiliation: Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China. dianwenju@fudan.edu.cn.
authors.forename: Dianwen
authors.initials: D
authors.lastname: Ju
mesh_terms: D001119:Arginase / Q000235:genetics / Q000633:toxicity*; D001343:Autophagy / Q000187:drug effects*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004847:Epithelial Cells / Q000187:drug effects* / Q000502:physiology*; D006801:Humans; D011994:Recombinant Proteins / Q000235:genetics / Q000633:toxicity
chemical_list: D011994:Recombinant Proteins; D001119:Arginase
keywords: Autophagy; Cytotoxicity; Laryngeal squamous cell carcinoma; Recombinant human arginase