Department of Medical Radiation Sciences, Institute of Clinical Sciences, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sahlgrenska Center for Cancer Research, Sahlgrenska Academy, University of Gothenburg, Gothenburg, Sweden.
Sci Rep. 2023 Apr 19;13(1):6417. doi: 10.1038/s41598-023-32091-9.
Recombinant α-microglobulin (A1M) is a proposed radioprotector during Lu-octreotate therapy of neuroendocrine tumors (NETs). To ensure a maintained therapeutic effect, we previously demonstrated that A1M does not affect the Lu-octreotate induced decrease in GOT1 tumor volume. However, the underlying biological events of these findings are still unknown. The aim of this work was to examine the regulation of apoptosis-related genes in GOT1 tumors short-time after i.v. administration of Lu-octreotate with and without A1M or A1M alone. Human GOT1 tumor-bearing mice received 30 MBq Lu-octreotate or 5 mg/kg A1M or co-treatment with both. Animals were sacrificed after 1 or 7 days. Gene expression analysis of apoptosis-related genes in GOT1 tissue was performed with RT-PCR. In general, similar expression patterns of pro- and anti-apoptotic genes were found after Lu-octreotate exposure with or without co-administration of A1M. The highest regulated genes in both irradiated groups compared to untreated controls were FAS and TNFSFRS10B. Administration of A1M alone only resulted in significantly regulated genes after 7 days. Co-administration of A1M did not negatively affect the transcriptional apoptotic response of Lu-octreotate in GOT1 tumors.
重组 α-微球蛋白(A1M)是神经内分泌肿瘤(NETs)Lu-奥曲肽治疗中一种潜在的辐射防护剂。为确保维持治疗效果,我们之前证明 A1M 不会影响 Lu-奥曲肽诱导的 GOT1 肿瘤体积减少。然而,这些发现的潜在生物学事件仍不清楚。本研究的目的是在 Lu-奥曲肽静脉给药后短期内,观察 GOT1 肿瘤中与凋亡相关的基因的调节,有无 A1M 或单独使用 A1M。携带 GOT1 肿瘤的人源化小鼠接受 30MBq Lu-奥曲肽或 5mg/kg A1M 或两者联合治疗。在第 1 天或第 7 天处死动物。采用 RT-PCR 法检测 GOT1 组织中与凋亡相关的基因表达。一般来说,在 Lu-奥曲肽暴露后有无 A1M 联合应用时,促凋亡和抗凋亡基因的表达模式相似。与未处理对照组相比,照射组中表达最高的基因是 FAS 和 TNFSFRS10B。单独给予 A1M 仅在第 7 天导致明显调节的基因。A1M 的联合应用并没有对 Lu-奥曲肽在 GOT1 肿瘤中的转录凋亡反应产生负面影响。