RT-qPCR analysis of apoptosis related genes in regrown GOT1-tumors in Balb/c NM after single or fractionated treatment regime of Lu-177-octreotate

ABSTRACT: We recently demonstrated that therapy with hyperfractionated administration of 177Lu-octreotate gave a larger volume reduction of GOT1 tumors compared to single administration of the same amount of radiopharmaceutical. The molecular mechanisms behind this response need to be examined. Transcriptional response in apoptotic-related genes have been found both early and late after treatment with 177Lu-octreotate suggesting that apoptosis-related responses appear also in tumor regrowth stage after treatment. The aims of this work were to compare the expression of genes involved in apoptosis in GOT1 tumors during growth phase from mice treated with 177Lu-octreotate and from untreated mice, and to compare gene expression in regrown GOT1 tumors from mice treated with single injection and hyperfractionated injections. The study was performed on tumor samples previously collected and analyzed by other methods. BALB/c mice, bearing the small-intestine neuroendocrine tumor GOT1, were divided into groups and treated i.v. with 2x15 MBq or 1x30; 2x30 or 1x60 MBq; 3x40, 2x60, or 1x120 MBq177Lu-octreotate. Controls were given saline. After tumor volume reduction and regrowth, the mice were euthanized and tumors were collected, and one part was prepared for IHC analysis, RNA was extracted from the other tumor tissue sample and analyzed by PCR Array for expression of 84 genes involved in apoptosis. Expression of each gene was compared with that in controls. Pathway analysis was performed from genes exhibiting at least 1.5-fold change in expression. The highest regulated gene, compared to untreated controls, was RIPK2 in the group that received 3x40 MBq of 177Lu-octreotate. The most frequently regulated gene among the groups in the study was the pro-apoptotic TNFSF8. Most genes in the study were upregulated. The │FC│-values were all below 3.5. The study present similarities and differences in molecular response between the groups of different 177Lu-octreotate treatments. The results point to a complexity that these studies bring and may have impact on the optimization of therapy in the future.

ORGANISM(S): Homo sapiens

PROVIDER: GSE250008 | GEO | 2025/12/08

REPOSITORIES: GEO