Multiple myeloma has always been an important health problem in human beings due to its high morbidity, high mortality, and lack of effective therapeutic drugs. This study investigated the anticancer effect and mechanism of the newly synthesized small molecule compound CPUC002 on multiple myeloma. Our results confirmed that CPUC002 inhibited proliferation and induced G0/G1 cell cycle arrest in multiple myeloma cells. Moreover, CPUC002 also induced apoptosis by mitochondrial pathway and exogenous pathway. In mechanism, CPUC002 triggered apoptosis by stabilizing p53 in NCI-H929 cells which expressed wt-p53. Knockdown of p53 partially suppressed CPUC002-induced apoptosis. This suggests that there are other molecular mechanisms underlying CPUC002’s antitumor effect. Further studies showed that the CPUC002 also inhibited the STAT3 signaling pathway, while knockdown of STAT3 abolished CPUC002-induced apoptosis and cell cycle arrest. In vivo, CPUC002 has significant antitumor activity through the same mechanism as our in vitro studies, and is highly safe in xenograft models. Together these findings indicate that CPUC002 induces apoptosis and G0/G1 cell cycle arrest in multiple myeloma cells by stabilizing p53 and inhibiting the STAT3 signaling pathway.

多发性骨髓瘤由于发病率高、死亡率高、缺乏有效的治疗药物，一直是人类面临的重要健康问题。本研究探讨了新合成的小分子化合物CPUC002对多发性骨髓瘤的抗癌作用及机制。我们的研究结果证实，CPUC002 在多发性骨髓瘤细胞中抑制增殖并诱导 G0/G1 细胞周期停滞。此外，CPUC002还通过线粒体途径和外源途径诱导细胞凋亡。在机制上，CPUC002 通过稳定表达 wt-p53 的 NCI-H929 细胞中的 p53 触发细胞凋亡。p53 的敲低部分抑制了 CPUC002 诱导的细胞凋亡。这表明 CPUC002 的抗肿瘤作用还有其他分子机制。进一步的研究表明，CPUC002 还抑制了 STAT3 信号通路，而 STAT3 的敲低消除了 CPUC002 诱导的细胞凋亡和细胞周期停滞。在体内，CPUC002通过与我们体外研究相同的机制具有显着的抗肿瘤活性，并且在异种移植模型中高度安全。这些发现共同表明 CPUC002 通过稳定 p53 和抑制 STAT3 信号通路诱导多发性骨髓瘤细胞凋亡和 G0/G1 细胞周期停滞。