caa a22 4500 605499721 CHVBK 20210128100552.0 cr unu---uuuuu 210128e20151001xx s 000 0 eng 10.1007/s00253-015-6565-6 doi (NATIONALLICENCE)springer-10.1007/s00253-015-6565-6 The role of autophagy in the cytotoxicity induced by recombinant human arginase in laryngeal squamous cell carcinoma [Elektronische Daten] [Chen Lin, Ziyu Wang, Li Li, Yong He, Jiajun Fan, Zhongyu Liu, Shuwei Zhao, Dianwen Ju] 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. Springer-Verlag Berlin Heidelberg, 2015 Autophagy nationallicence Recombinant human arginase nationallicence Laryngeal squamous cell carcinoma nationallicence Cytotoxicity nationallicence Lin Chen Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut Wang Ziyu Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut Li Li Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut He Yong Department of Otolaryngology, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang Province, China aut Fan Jiajun Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut Liu Zhongyu Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut Zhao Shuwei Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut Ju Dianwen Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8487-8494 0175-7598 99:20<8487 2015 99 253 https://doi.org/10.1007/s00253-015-6565-6 text/html Onlinezugriff via DOI BK010053 XK010053 XK010000 Metadata rights reserved Springer special CC-BY-NC licence nationallicence 1 research-article jats NATIONALLICENCE NATIONALLICENCE NL-springer NATIONALLICENCE 856 40 https://doi.org/10.1007/s00253-015-6565-6 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Lin Chen Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut NATIONALLICENCE 700 1- Wang Ziyu Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut NATIONALLICENCE 700 1- Li Li Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut NATIONALLICENCE 700 1- He Yong Department of Otolaryngology, The Affiliated Hospital of School of Medicine of Ningbo University, Ningbo, Zhejiang Province, China aut NATIONALLICENCE 700 1- Fan Jiajun Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut NATIONALLICENCE 700 1- Liu Zhongyu Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut NATIONALLICENCE 700 1- Zhao Shuwei Department of Otolaryngology, Changzheng Hospital, Second Military Medical University, 200003, Shanghai, China aut NATIONALLICENCE 700 1- Ju Dianwen Department of Biosynthesis & Key Lab of Smart Drug Delivery of Ministry of Education, School of Pharmacy, Fudan University, Shanghai, China aut NATIONALLICENCE 773 0- Applied Microbiology and Biotechnology Springer Berlin Heidelberg 99/20(2015-10-01), 8487-8494 0175-7598 99:20<8487 2015 99 253