Background: Rituximab is a chimeric monoclonal antibody against CD20. It is an established immunotherapeutic agent for non-Hodgkin's lymphoma. Even though rituximab has been used in clinics for decades, only 50% of the patients respond to rituximab therapy. To enhance the in vitro effect of rituximab, it was labeled with Iodine-131 (¹³¹I) and combined effect of ¹³¹I-rituximab and camptothecin (CPT) was studied on a tumor cell line expressing CD20.
Objective: The aim is to study the magnitude of cell killing and the underlying mechanism responsible for enhancing in vitro therapeutic efficacy.
Materials and Methods: Rituximab was labeled with ¹³¹I by the iodogen method. Raji cells were pretreated with CPT (250 nM) for an hour followed by ¹³¹I-rituximab (0.37 and 3.7 MBq) and incubated for 24 h in a humidified atmosphere of CO₂ incubator at 37°C. Subsequently, Raji cells were harvested and thoroughly washed to carry out studies of cellular toxicity, apoptosis, cell cycle, and mitogen-activated protein kinase (MAPK) pathways.
Results: Maximal inhibition of cell proliferation and enhancement of apoptotic cell death was observed in the cells treated with the combination of CPT and ¹³¹I-rituximab, compared to controls of CPT-treated and ¹³¹I-rituximab-treated cells. Raji cells undergo G1 arrest after ¹³¹I-rituximab treatment, which leads to apoptosis and was confirmed by the downregulation of bcl_xl protein. Expression of p38 was decreased while an increase in phosphorylation of p38 was observed in the combination treatment of CPT and ¹³¹I-rituximab.
Conclusions: It was concluded from the findings that CPT enhanced ¹³¹I-rituximab-induced apoptosis, G1 cell cycle arrest and p38 MAPK phosphorylation in Raji cells.


中文翻译：

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喜树碱增强 131I-利妥昔单抗诱导的 Burkitt 淋巴瘤细胞 G1 期阻滞和凋亡


背景：利妥昔单抗是一种针对 CD20 的嵌合单​​克隆抗体。它是一种既定的非霍奇金淋巴瘤免疫治疗剂。尽管利妥昔单抗已在临床中使用了数十年，但只有 50% 的患者对利妥昔单抗治疗有反应。为了增强利妥昔单抗的体外作用，它用碘131 ( ¹³¹ I) 标记，并研究了¹³¹ I-利妥昔单抗和喜树碱(CPT) 对表达CD20 的肿瘤细胞系的联合作用。
目的：目的是研究细胞杀伤的程度和增强体外治疗效果的潜在机制。
材料与 方法：利妥昔单抗标记为¹³¹我用碘剂法。用 CPT (250 nM) 预处理 Raji 细胞 1 小时，然后用¹³¹ I-利妥昔单抗 (0.37 和 3.7 MBq) 并在 37°C的 CO _{2培养箱的湿润气氛中培养 24 小时。}随后，收获 Raji 细胞并彻底清洗以进行细胞毒性、细胞凋亡、细胞周期和丝裂原活化蛋白激酶 (MAPK) 途径的研究。
结果：与用 CPT 处理和¹³¹ I-利妥昔单抗处理的细胞相比，在用 CPT 和¹³¹ I-利妥昔单抗联合处理的细胞中观察到细胞增殖的最大抑制和凋亡细胞死亡的增强。^{Raji 细胞在131}后经历 G1 期阻滞I-rituximab 治疗导致细胞凋亡，并通过 bcl _xl蛋白的下调得到证实。^{在 CPT 和131} I-利妥昔单抗的联合治疗中观察到 p38 的表达降低，而 p38 的磷酸化增加。
结论：从研究结果得出的结论是，CPT 增强了 Raji 细胞中¹³¹ I-利妥昔单抗诱导的细胞凋亡、G1 细胞周期停滞和 p38 MAPK 磷酸化。