The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasophary
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ORIGINAL ARTICLE
The role of Caspase-1/GSDMD-mediated pyroptosis in Taxol-induced cell death and a Taxol-resistant phenotype in nasopharyngeal carcinoma regulated by autophagy Xianyao Wang & Heqing Li & Wei Li & Jun Xie & Fengjun Wang & Xiaowei Peng & Yexun Song & Guolin Tan Received: 16 September 2019 / Accepted: 24 January 2020 # Springer Nature B.V. 2020
Abstract Taxol has been widely used as a first-line chemotherapeutic agent for the treatment of advanced nasopharyngeal carcinoma (NPC). However, acquired drug resistance has caused great difficulties in clinical treatment. Pyroptosis is a newly discovered programmed cell death pathway, and Caspase-1 and gasdermin D (GSDMD) play key roles in driving canonical pyroptosis. Increasing evidence suggests that
pyroptosis is associated with the development of cancer; however, the function and mechanism of pyroptosis in NPC remain obscure. In this study, we observed that Taxol treatment caused pyroptotic cell death, along with activation of Caspase-1 and maturation of IL-1β, as well as cleavage of GSDMD, which is the canonical pyroptosis executor. Furthermore, Taxol-induced pyroptotic cell death could be suppressed by Caspase-
Taxol induced pyroptosis in NPC cell lines. • Taxol treatment results in Caspase-1/GSDMD–mediated canonical pyroptosis, but not noncanonical pyroptosis. • Inhibition of Caspase-1 activation could induce a taxol-resistant phenotype. • GSDMD-knockout induced a taxol-resistant phenotype in vitro and in vivo. • Caspase-1/GSDMD-mediated pyroptotic cell death could be downregulated by autophagy. Electronic supplementary material The online version of this article (https://doi.org/10.1007/s10565-020-09514-8) contains supplementary material, which is available to authorized users. X. Wang : H. Li : W. Li : Y. Song (*) : G. Tan (*) Department of Otolaryngology-Head Neck Surgery, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan Province, China e-mail: [email protected] e-mail: [email protected]
W. Li Department of Clinical Laboratory, The Third Xiangya Hospital of Central South University, Changsha 410013 Hunan Province, China
J. Xie Department of Otolaryngology-Head Neck Surgery, The Hunan Children’s Hospital, Changsha 410013 Hunan Province, China F. Wang : Y. Song Department of Otolaryngology-Head Neck Surgery, The Xiangya Hospital of Central South University, Changsha 410013 Hunan Province, China X. Peng Department of Oncology Plastic Surgery, Hunan Province Cancer Hospital, Changsha 410007 Hunan Province, China
Cell Biol Toxicol
1 inhibitor (Z-YVAD-FMK) and GSDMD knockout. Moreover, NPC parental cells demonstrated higher levels of pyroptosis than Taxol-resistant cells, and pyroptosis mediated by Caspase-1/GSDMD suppression induced by a Caspase-1 inhibitor and GSDMD knockout could induce a Taxol-resistant phenotype in vitro and in vivo. By transfecting an siRNA targeting Beclin-1 into NPC Taxol-resistant cells, we discovered that autophagy could negatively regulate pyroptosis by inhibiting Caspase-1/GSDMD ac
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