Artesunate synergistically promotes sorafenib‑induced apoptosis and ferroptosis in non‑Hodgkin lymphoma cells through inhibition of the STAT3 pathway

作者：Yingying Chen, Huan Tao, Fujue Wang, Pengqiang Wu, Jie Gao, Xue Zhang, Zhengcang He, Zhencang Zhou, Yongqian Jia · 发表于：Oncology Reports · 年份：2023 · DOI：10.3892/or.2023.8584 · 被引用次数：27 · 研究领域：Ferroptosis and cancer prognosis、RNA modifications and cancer、Lymphoma Diagnosis and Treatment

Despite the development of advanced therapies, the prognosis of non‑Hodgkin lymphoma (NHL) remains unsatisfactory due to refractory and relapsed cases. Artesunate (ART) and sorafenib (SOR) both exert potential antitumor activity in lymphoma. The present study aimed to investigate whether ART and SOR produce synergistic anti‑lymphoma effects, and to determine the potential underlying mechanisms. Cell viability assay, flow cytometry, malondialdehyde assay, GSH assay and western blotting were performed to evaluate cell viability, and changes in apoptosis, autophagic vacuoles, reactive oxygen species, mitochondrial membrane potential, lipid peroxidation and protein expression. The results demonstrated that ART and SOR synergistically inhibited the viability of NHL cells. ART and SOR also synergistically induced apoptosis, and markedly increased the expression levels of cleaved caspase‑3 and poly (ADP‑ribose) polymerase. Mechanistically, ART and SOR synergistically induced autophagy, and rapamycin enhanced the ART‑ or SOR‑induced inhibition of cell viability. Furthermore, it was demonstrated that ferroptosis promoted ART‑ and SOR‑induced cell death through increasing lipid peroxides. Erastin enhanced the inhibitory effects of ART and SOR on cell viability, whereas ferrostatin‑1 reduced the ART‑ and SOR‑induced apoptosis of SU‑DHL4 cells. Further studies revealed that signal transducer and activator of transcription 3 (STAT3) contributed to ferroptosis induced by ART and SOR in NHL...