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促性腺激素释放激素对促肾上腺皮质激素腺瘤细胞系细胞增殖的影响。

Effects of Oxytocin on Cell Proliferation in a Corticotroph Adenoma Cell Line.

机构信息

Department of Internal Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

Institute of Evidence-based Medicine, Yonsei University Wonju College of Medicine, Wonju, Korea.

出版信息

Endocrinol Metab (Seoul). 2019 Sep;34(3):302-313. doi: 10.3803/EnM.2019.34.3.302.

DOI:10.3803/EnM.2019.34.3.302
PMID:31565883
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC6769335/
Abstract

BACKGROUND

Oxytocin (OXT) has been reported to act as a growth regulator in various tumor cells. However, there is a paucity of data on the influence of OXT on cell proliferation of corticotroph adenomas. This study aimed to examine whether OXT affects cell growth in pituitary tumor cell lines (AtT20 and GH3 cells) with a focus on corticotroph adenoma cells.

METHODS

Reverse transcription polymerase chain reaction and enzyme-linked immunosorbent assay were conducted with AtT20 cells to confirm the effects of OXT on hormonal activity; flow cytometry was used to assess changes in the cell cycle after OXT treatment. Moreover, the impact of OXT on proliferating cell nuclear antigen (PCNA), nuclear factor κB, and mitogen-activated protein kinase signaling pathway was analyzed by Western blot.

RESULTS

OXT treatment of 50 nM changed the gene expression of OXT receptor and pro-opiomelanocortin within a short time. In addition, OXT significantly reduced adrenocorticotropic hormone secretion within 1 hour. S and G2/M populations of AtT20 cells treated with OXT for 24 hours were significantly decreased compared to the control. Furthermore, OXT treatment decreased the protein levels of PCNA and phosphorylated extracellular-signal-regulated kinase (P-ERK) in AtT20 cells.

CONCLUSION

Although the cytotoxic effect of OXT in AtT20 cells was not definite, OXT may blunt cell proliferation of corticotroph adenomas by altering the cell cycle or reducing PCNA and P-ERK levels. Further research is required to investigate the role of OXT as a potential therapeutic target in corticotroph adenomas.

摘要

背景

催产素（OXT）已被报道在各种肿瘤细胞中作为生长调节剂发挥作用。然而，关于 OXT 对促肾上腺皮质腺瘤细胞增殖的影响的数据很少。本研究旨在研究 OXT 是否会影响垂体瘤细胞系（AtT20 和 GH3 细胞）中的细胞生长，重点是促肾上腺皮质腺瘤细胞。

方法

采用 AtT20 细胞进行逆转录聚合酶链反应和酶联免疫吸附试验，以确认 OXT 对激素活性的影响；采用流式细胞术评估 OXT 处理后细胞周期的变化。此外，通过 Western blot 分析 OXT 对增殖细胞核抗原（PCNA）、核因子 κB 和丝裂原活化蛋白激酶信号通路的影响。

结果

50 nM 的 OXT 处理在短时间内改变了 OXT 受体和 pro-opiomelanocortin 的基因表达。此外，OXT 在 1 小时内显著减少促肾上腺皮质激素的分泌。与对照组相比，OXT 处理 24 小时的 AtT20 细胞的 S 和 G2/M 期明显减少。此外，OXT 处理降低了 AtT20 细胞中 PCNA 和磷酸化细胞外信号调节激酶（P-ERK）的蛋白水平。

结论

尽管 OXT 在 AtT20 细胞中的细胞毒性作用并不明确，但 OXT 可能通过改变细胞周期或降低 PCNA 和 P-ERK 水平来抑制促肾上腺皮质腺瘤细胞的增殖。需要进一步研究以探讨 OXT 作为促肾上腺皮质腺瘤潜在治疗靶点的作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/b3c03ad0a967/enm-34-302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/7b15b7973fef/enm-34-302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/015b1fe262c0/enm-34-302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/0dadeaa354e6/enm-34-302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/c7f172470785/enm-34-302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/f4e0b9b687d8/enm-34-302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/b3c03ad0a967/enm-34-302-g006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/7b15b7973fef/enm-34-302-g001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/015b1fe262c0/enm-34-302-g002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/0dadeaa354e6/enm-34-302-g003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/c7f172470785/enm-34-302-g004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/f4e0b9b687d8/enm-34-302-g005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f7b1/6769335/b3c03ad0a967/enm-34-302-g006.jpg

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