The STAT3 inhibitor stattic overcome bortezomib-resistance in multiple myeloma via decreasing PSMB6

Bortezomib, an FDA approved drug in 2003 for newly diagnosed and relapsed/refractory MM, had showed great efficacy in different clinical settings. However, many patients still developed resistance to Bortezomib, and the mechanism of action remains unelucidated. Here, we showed that Bortezomib resist...

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Bibliographic Details
Published in:Experimental cell research 2023-08, Vol.429 (1), p.113634-113634, Article 113634
Main Authors: Yuan, Canli, Yuan, Mei, Li, Wenyu, Cheng, Hai, Luo, Jianping, Zhang, Qi, Shi, Mengya, Niu, Mingshan, Yang, Jiajia, Sun, Zengtian, Yan, Zhiling, Xu, Kailin, Li, Zhenyu, Yao, Yao
Format: Article
Language:English
Subjects:
Antineoplastic Agents - pharmacology
Antineoplastic Agents - therapeutic use
Apoptosis - genetics
Bortezomib - pharmacology
Bortezomib-resistance
Cell Line, Tumor
Drug Resistance, Neoplasm - genetics
Humans
Multiple myeloma
Multiple Myeloma - drug therapy
Multiple Myeloma - genetics
Multiple Myeloma - metabolism
PSMB6
STAT3
STAT3 Transcription Factor - genetics
STAT3 Transcription Factor - metabolism
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Summary:Bortezomib, an FDA approved drug in 2003 for newly diagnosed and relapsed/refractory MM, had showed great efficacy in different clinical settings. However, many patients still developed resistance to Bortezomib, and the mechanism of action remains unelucidated. Here, we showed that Bortezomib resistance can be partially overcome by targeting a different subunit of 20 S complex - PSMB6. PSMB6 knock down by shRNA increased sensitivity to Bortezomib in resistant and sensitive cell line. Interestingly, a STAT3 inhibitor, Stattic, is shown to selectively inhibit PSMB6 and induce apoptosis in Bortezomib resistant and sensitive MM cells, even with IL-6 induction. Therefore, PSMB6 is a novel target for Bortezomib resistance and Stattic may offer a potential therapeutic strategy.
ISSN:0014-4827
1090-2422
DOI:10.1016/j.yexcr.2023.113634