Department of Hematology, The First Affiliated Hospital of Chongqing Medical University.
Department of Respiratory, The First Affiliated Hospital of Chongqing Medical University.
Tohoku J Exp Med. 2022 Jul 22;257(4):315-326. doi: 10.1620/tjem.2022.J044. Epub 2022 May 27.
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.
多发性骨髓瘤（MM）是一种常见的血液恶性肿瘤。硼替佐米（BTZ）是一种用于 MM 治疗的传统药物，但目前的治疗方法存在局限性。三氟拉嗪（TFP）是一种用于治疗急、慢性精神病的临床药物。最近，研究人员发现 TFP 可以抑制多种癌症的肿瘤生长。我们试图研究 BTZ 和 TFP 对体内和体外 MM 的影响。我们通过细胞计数试剂盒-8 检测、EdU 检测、western blot 和流式细胞术，集中研究了 BTZ 和 TFP 对 MM 细胞增殖和凋亡的单独和联合影响。我们发现联合治疗对 MM 细胞有很强的协同作用。联合治疗可诱导 MM 细胞在 G2/M 期停滞并诱导细胞凋亡。同时，BTZ 联合 TFP 通过 MM.1s 异种移植肿瘤模型在体内发挥更好的抗 MM 作用。此外，我们还探讨了 TFP 诱导 MM 细胞凋亡的机制，我们注意到 TFP 可能通过抑制 p-P38 MAPK/NUPR1 诱导 MM 细胞凋亡。综上所述，我们的研究结果表明，TFP 可协同增强 BTZ 诱导的多发性骨髓瘤抗癌作用，这可能是 MM 治疗的一种有前途的治疗策略。
