Dokuz Eylül University, Vocational School of Health Services,İzmir, Turkey; Department of Otorhinolaryngology Unit of Hearing Speech and Balance, Dokuz Eylül University Hospital, İzmir, Turkey; Department of Basic Oncology, Dokuz Eylül University, Institute of Oncology, İzmir, Turkey.
Department of Otorhinolaryngology, Dokuz Eylül University Faculty of Medicine, İzmir, Turkey.
J Int Adv Otol. 2022 Sep;18(5):392-398. doi: 10.5152/iao.2022.21268.
This study aimed to compare the cytotoxic, cytostatic, and ototoxic effects of lipoplatin compared to cisplatin application in the subcutaneous xenograft nude mouse neuroblastoma tumor model.
In this study, C1300 neuroblastoma cells were administered subcutaneously to 21 male nude mice. When the tumor reached 150 mm3 diameter, mice were randomized into 3 groups. Saline, cisplatin, and lipoplatin were given intraperitoneally. The auditory function tests were performed before administration and 72 hours after administration. Mice were sacrificed and the tumor and cochlea were removed after 72 hours. Histopathologic evaluation of necrosis and apoptosis was determined by the TdT-mediated dUTP-biotin nick end labeling (TUNEL) method. Cyclooxygenase 2, superoxide dismutase 2, and inducible nitric oxide synthase levels were determined by immunohistochemistry in tissue samples.
Apoptosis and necrosis rates were higher in lipoplatin group than in cisplatin group (P=.035 and P=.010, respectively) in tumor tissue. In the spiral ganglion, apoptosis and necrosis were lower in the lipoplatin group than in cisplatin group (P=.002 and P=.002, respectively). Cyclooxygenase 2 pattern in the cochlea was positive in both control and lipoplatin group and negative in cisplatin group (P=.001). Superoxide dismutase 2 and inducible nitric oxide synthase 2 protein expressions showed no difference between groups. The auditory functions were similar to baseline values and had a better threshold value in lipoplatin group than cisplatin group.
For the treatment of neuroblastoma, the use of lipoplatin seems to be beneficial in reducing side effects of cisplatin. We recommend that the mechanism of these properties of lipoplatin should be evaluated in further studies.
本研究旨在比较 lipoplatin 与 cisplatin 在皮下异种移植裸鼠神经母细胞瘤肿瘤模型中的细胞毒性、细胞抑制和耳毒性作用。
在这项研究中，将 C1300 神经母细胞瘤细胞皮下注射到 21 只雄性裸鼠中。当肿瘤达到 150mm3 直径时，将小鼠随机分为 3 组。腹腔内给予生理盐水、顺铂和 lipoplatin。在给药前和给药后 72 小时进行听觉功能测试。给药 72 小时后，处死小鼠并取出肿瘤和耳蜗。通过 TdT 介导的 dUTP-生物素缺口末端标记（TUNEL）法确定组织坏死和凋亡的组织病理学评估。通过免疫组织化学法测定组织样本中环氧化酶 2、超氧化物歧化酶 2 和诱导型一氧化氮合酶水平。
肿瘤组织中 lipoplatin 组的细胞凋亡和坏死率高于 cisplatin 组（分别为 P=.035 和 P=.010）。螺旋神经节中，lipoplatin 组的细胞凋亡和坏死率低于 cisplatin 组（分别为 P=.002 和 P=.002）。耳蜗中环氧化酶 2 模式在对照组和 lipoplatin 组中均为阳性，在 cisplatin 组中为阴性（P=.001）。超氧化物歧化酶 2 和诱导型一氧化氮合酶 2 蛋白表达在各组之间无差异。与基线值相比，听觉功能相似，lipoplatin 组的阈值优于 cisplatin 组。
对于神经母细胞瘤的治疗，使用 lipoplatin 似乎可以降低 cisplatin 的副作用。我们建议在进一步的研究中评估 lipoplatin 这些特性的机制。
