Tohoku J. Exp. Med., 2022 August, 257(4)

Trifluoperazine Synergistically Potentiates Bortezomib-Induced Anti-Cancer Effect in Multiple Myeloma via Inhibiting P38 MAPK/NUPR1

Zizi Jing,¹ Wei Yu,¹ Anmao Li,² Xuanxin Chen,¹ Yuying Chen¹ and Jianbin Chen¹

¹Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China
²Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University, Chongqing, China

Multiple myeloma (MM) is a common hematological malignancy. Bortezomib (BTZ) is a traditional medicine for MM treatment, but there are limitations for current treatment methods. Trifluoperazine (TFP) is a clinical drug for acute and chronic psychosis therapy. Lately, researchers have found that TFP can suppress tumor growth in many cancers. We attempted to study the effects of BTZ and TFP on MM in vivo and in vitro. We concentrated on the individual and combined impact of BTZ and TFP on the proliferation and apoptosis of MM cells via Cell Counting kit-8 assay, EdU assay, western blot, and flow cytometry. We found that combination therapy has a strong synergistic impact on MM cells. Combination therapy could induce cell arrest during G2/M phase and induce apoptosis in MM cells. Meanwhile, BTZ combined with TFP could play a better role in the anti-MM effect in vivo through MM.1s xenograft tumor models. Furthermore, we explored the mechanism of TFP-induced apoptosis in MM, and we noticed that TFP might induce MM apoptosis by inhibiting p-P38 MAPK/NUPR1. In summary, our findings suggest that TFP could synergistically enhance the BTZ-induced anti-cancer effect in multiple myeloma, which might be a promising therapeutic strategy for MM treatment.

Keywords —— apoptosis; bortezomib; cell cycle; multiple myeloma; trifluoperazine

© 2022 Tohoku University Medical Press

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Tohoku J. Exp. Med 2022, 257, 315-326.

Correspondence: Jianbin Chen, Department of Hematology, The First Affiliated Hospital of Chongqing Medical University, No 1 YouYi Road, Yuzhong, Chongqing 400016, People’s Republic of China.

e-mail: cqchejianbin2007@126.com