探索牛磺罗定对小鼠骨肉瘤模型中肿瘤重量和微血管密度的影响。
Exploring the effects of taurolidine on tumor weight and microvessel density in a murine model of osteosarcoma.
发表日期:2024
作者:
Lisanne K A Neijenhuis, Leuta L Naumann, Sonia A M Ferkel, Samuel J S Rubin, Stephan Rogalla
来源:
Cell Death & Disease
摘要:
骨肉瘤是最常见的恶性原发性骨肿瘤。尽管化疗最近取得了进展,但患有播散性疾病的患者的预后仍然很差。此外,目前的治疗方案存在严重副作用的显着风险。因此,对具有改进的安全性的有效疗法的临床需求尚未得到满足。牛磺罗定是一种抗菌剂,已被证明可诱导不同类型癌细胞系的细胞死亡。在这项研究中,我们检查了牛磺罗定在骨肉瘤动物模型中的抗肿瘤和抗血管生成作用。在第 0 天,将 K7M2 鼠骨肉瘤细胞肌内和腹膜内注射到 60 只 BALB/c 小鼠中。然后将动物随机接受 2% 牛磺罗定 (800 mg/kg)、1% 牛磺罗定 (400 mg/kg) 或 0.9% 氯化钠对照静脉或腹膜内给药治疗 7 天。 35 天后,对小鼠实施安乐死,并收获肿瘤进行分析。由于并发症,十八只小鼠被排除在分析之外。从第9天到第21天,2%牛磺罗定腹腔注射治疗组的体重显着降低,这与该组死亡率升高一致。与对照组相比,1% (p = 0.003) 和 2% (p = 0.006) 腹膜内牛磺罗定治疗组的腹膜内肿瘤重量显着降低。牛磺罗定对肌内肿瘤或静脉内给药没有观察到抗肿瘤作用。治疗组之间的微血管密度或有丝分裂率没有显着差异。 2%牛磺罗定腹腔注射组的体重减轻和死亡率升高表明,较低的1%剂量是优选的。 总之,没有抗血管生成活性的证据,并且本研究中观察到的牛磺罗定对骨肉瘤的抗肿瘤作用是有限的。此外,其毒性特征值得进一步评估。鉴于这些观察结果,有必要进一步研究以完善牛磺罗定在骨肉瘤治疗中的使用。© 2024 Neijenhuis 等人。
Osteosarcoma is the most common malignant primary bone tumor. The prognosis for patients with disseminated disease remains very poor despite recent advancements in chemotherapy. Moreover, current treatment regimens bear a significant risk of serious side effects. Thus, there is an unmet clinical need for effective therapies with improved safety profiles. Taurolidine is an antibacterial agent that has been shown to induce cell death in different types of cancer cell lines.In this study, we examined both the antineoplastic and antiangiogenic effects of taurolidine in animal models of osteosarcoma. K7M2 murine osteosarcoma cells were injected, both intramuscular and intraperitoneal, into 60 BALB/c mice on day zero. Animals were then randomized to receive treatment with taurolidine 2% (800 mg/kg), taurolidine 1% (400 mg/kg), or NaCl 0.9% control for seven days by intravenous or intraperitoneal administration.After 35 days, mice were euthanized, and the tumors were harvested for analysis. Eighteen mice were excluded from the analysis due to complications. Body weight was significantly lower in the 2% taurolidine intraperitoneal treatment group from day 9 to 21, consistent with elevated mortality in this group. Intraperitoneal tumor weight was significantly lower in the 1% (p = 0.003) and 2% (p = 0.006) intraperitoneal taurolidine treatment groups compared to the control. No antineoplastic effects were observed on intramuscular tumors or for intravenous administration of taurolidine. There were no significant differences in microvessel density or mitotic rate between treatment groups. Reduced body weight and elevated mortality in the 2% taurolidine intraperitoneal group suggest that the lower 1% dose is preferable.In conclusion, there is no evidence of antiangiogenic activity, and the antitumor effects of taurolidine on osteosarcoma observed in this study are limited. Moreover, its toxic profile grants further evaluation. Given these observations, further research is necessary to refine the use of taurolidine in osteosarcoma treatment.© 2024 Neijenhuis et al.