Abstract:
:The destruction of proteins via the ubiquitin-proteasome system is a multi-step, complex process involving polyubiquitination of substrate proteins, followed by proteolytic degradation by the macromolecular 26S proteasome complex. Inhibitors of the proteasome promote the accumulation of proteins that are deleterious to cell survival and are promising anticancer agents. Oprozomib (OPZ), an oral second-generation proteasome inhibitor, has been shown to inhibit the growth of several cancers in preclinical and clinical trials, including multiple myeloma and head and neck cancers, but its effects on lung cancer has not yet been determined. In this study, we evaluated the inhibitory effects of OPZ on lung cancer cell lines in vitro. The results showed that OPZ significantly suppressed cell proliferation and strongly induced apoptosis in both tested lung cancer cells independent of p53 expression. OPZ was able to cause obvious caspase 3 and PARP cleavages and stabilize p53 and its transcriptional targets p21, PUMA, and Noxa. Moreover, OPZ was capable of sensitizing lung cancer cells to the conventional chemotherapeutic drug cisplatin. Our study provides preclinical data and sheds light on the potential applications of proteasome inhibitor OPZ in lung cancer treatment.
journal_name
Acta Biochim Biophys Sin (Shanghai)journal_title
Acta biochimica et biophysica Sinicaauthors
Zhu H,Wang T,Xin Z,Zhan Y,Gu G,Li X,Wang X,Yang S,Liu Cdoi
10.1093/abbs/gmz093subject
Has Abstractpub_date
2019-09-06 00:00:00pages
1034-1040issue
10eissn
1672-9145issn
1745-7270pii
5565031journal_volume
51pub_type
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