利妥昔单抗 (RTX) 耐药性是治疗弥漫性大 B 细胞淋巴瘤 (DLBCL) 的一个显着挑战。 β-谷甾醇 (β-ST) 是一种植物甾醇，存在于多种水果、香料和药用植物中。 β-ST 的抗肿瘤特性已在多种实体恶性肿瘤中得到证实；然而，它对 DLBCL 的影响尚不清楚。本研究探讨了 β-ST 在 DLBCL 中的作用及其潜在机制。我们的研究结果表明，β-ST 以浓度和时间依赖性方式阻碍 DLBCL 细胞增殖。 β-ST 似乎可以改变鞘脂代谢，促进酸性鞘磷脂酶 (ASM) 易位到质膜，通过增加神经酰胺合成来增强神经酰胺平台，从而诱导 DLBCL 细胞凋亡。此外，我们发现 RTX 在体外启动细胞凋亡和存活途径，前者取决于 ASM 的瞬时激活，而 β-ST 可以通过调节 ASM/神经酰胺 (Cer) 信号传导来增强 RTX 的抗 DLBCL 功效。总的来说，我们的研究结果阐明了 β-ST 在 DLBCL 中的机制作用，并强调了其通过 ASM 激活放大 RTX 抗肿瘤功效的潜力，提出了提高 RTX 治疗疗效的潜在途径。

Rituximab (RTX) resistance is a notable challenge in treating diffuse large B-cell lymphoma (DLBCL). β-Sitosterol (β-ST) is a plant sterol that has been found in a broad variety of fruits, spices, and medicinal plants. The antineoplastic properties of β-ST are established in various solid malignancies; however, its effect on DLBCL is uncharted. This study investigates the role of β-ST in DLBCL as well as the underlying mechanisms. Our findings indicated that β-ST impeded DLBCL cell proliferation in a concentration- and time-dependent manner. β-ST appeared to alter sphingolipid metabolism, facilitate acid sphingomyelinase (ASM) translocation to the plasma membrane, augment ceramide platforms through increased ceramide synthesis, and consequently induce apoptosis in DLBCL cells. Furthermore, we found that RTX initiated both apoptotic and survival pathways in vitro, with the former contingent on the transient activation of the ASM, and β-ST could amplify the anti-DLBCL efficacy of RTX by modulating ASM/Ceramide (Cer) signaling. Collectively, our findings elucidate the mechanistic role of β-ST in DLBCL and underscore its potential in amplifying the antineoplastic efficacy of RTX via ASM activation, proposing a potential avenue to improve the efficacy of RTX therapy.