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 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 ther-apeutic strategy.

Automated summary

It was found that targeting the PSMB6 subunit of the 20 S complex could partially overcome resistance to Bortezomib, and the STAT3 inhibitor Stattic was shown to selectively inhibit PSMB6 and induce apoptosis in Bortezomib resistant and sensitive multiple myeloma cells. Therefore, PSMB6 may be a novel target for overcoming Bortezomib resistance, and Stattic may offer a potential therapeutic strategy.