生长抑素对 TNF 受体和肝细胞癌细胞株凋亡的不同影响

IF 1.5 Q3 GASTROENTEROLOGY & HEPATOLOGY
M. Georgiadou, George Notas, Ioannis Tsomidis, Argyro Voumbouraki, Ioannis Drygiannakis, George Emmanouil, E. Kouroumalis
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引用次数: 0

摘要

在动物实验和人体肿瘤中都证明了体生长抑素的抗肿瘤活性。临床试验报告的结果相互矛盾。因此,我们推测,体生长抑素可能对不同的肝癌细胞有不同的作用。明确这些作用可能有助于更好地选择适合最佳治疗效果的患者。我们使用 HepG2 和 Hep3B 人肝癌细胞在与体生长激素类似物奥曲肽培养后,研究了 TNF 受体的 mRNA 和蛋白表达以及 TNFa 诱导的细胞凋亡。对 RT-PCR、Western 印迹以及与细胞凋亡相关的参数(NF-kB 核转位、P65 Ser536 和 P65 Ser468 磷酸化、DNA 断裂)进行了评估。两种细胞系中只有 TNFR1 是组成型的。与 Hep3B 细胞相比,奥曲肽孵育导致 HepG2 细胞的 TNFR1 mRNA 和蛋白质更早减少(分别为 1 小时和 6-12 小时)。TNFa 诱导 NF-kB 转位至细胞核,在 Hep3B 中更为明显。转位不受奥曲肽的影响。丝氨酸磷酸化受 TNFa 诱导明显,在 Hep3B 细胞中更为明显。TNFa诱导的丝氨酸536磷酸化仅在HepG2细胞中受到奥曲肽的抑制。在HepG2细胞中,奥曲肽或TNFa都不会影响DNA片段化,但在Hep3B细胞中,TNFa会诱导DNA片段化(增加1.8倍),TUNEL指数(43,而HepG2细胞为19)证实了这一点。奥曲肽和 TNFa 共同作用可诱导 HepG2 细胞凋亡(与对照组相比增加 1.7 倍),但可抑制 Hep3B 细胞凋亡。我们得出以下结论(1)奥曲肽降低了两种细胞系中 TNFR1 受体的表达;(2)奥曲肽对两种细胞系中细胞凋亡的参数产生了不同的影响;(3)这可能是在人类肝细胞癌试验中,体生长激素类似物治疗结果相互矛盾的部分原因。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Differential Effects of Somatostatin on TNF Receptors and Apoptosis in Hepatocellular Carcinoma Cell Lines
The anti-tumoral activity of somatostatin has been demonstrated in both animal experiments and human tumors. Clinical trials have reported conflicting results. We therefore hypothesized that somatostatin might have different effects in various hepatocellular carcinoma cells. Their clarification would possibly allow for the better selection of patients suitable for the optimal treatment results. We studied the mRNA and protein expression of TNF receptors and the TNFa-induced apoptosis using the HepG2 and the Hep3B human hepatocellular carcinoma cells after incubation with the somatostatin analog octreotide. RT-PCR, Western blot, and parameters associated with apoptosis (NF-kB nuclear translocation, P65 Ser536 and P65 Ser468 phosphorylation, DNA fragmentation) were assessed. Only TNFR1 was constitutively present in the two cell lines. Octreotide incubation led to an earlier reduction in TNFR1 mRNA and protein in HepG2 compared to Hep3B cells (1 h and 6–12 h, respectively). NF-kB translocation to the nucleus was induced by TNFa and was more prominent in Hep3B. Translocation was unaffected by octreotide. Serine phosphorylation was significantly induced by TNFa and was more evident in the Hep3B cells. TNFa-induced Ser536 phosphorylation was inhibited by octreotide only in the HepG2 cells. DNA fragmentation was not influenced by either octreotide or TNFa in the HepG2 cells, but TNFa induced fragmentation in the Hep3B cells (1.8-fold increase) verified by the TUNEL index (43 compared to 19 for the HepG2 cells). Octreotide and TNFa co-incubation induced apoptosis in the HepG2 cells (1.7-fold increase compared to controls) but inhibited apoptosis in the Hep3B cells. We conclude that: (1) octreotide reduced TNFR1 receptor expression in both cell lines, (2) parameters of apoptosis were differentially affected by octreotide in the two cell lines, and (3) this might be a partial explanation for the conflicting results of somatostatin analog treatment in human hepatocellular carcinoma trials.
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来源期刊
Gastroenterology Insights
Gastroenterology Insights GASTROENTEROLOGY & HEPATOLOGY-
CiteScore
2.80
自引率
3.40%
发文量
35
审稿时长
10 weeks
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