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全反式维甲酸和紫杉醇对常染色体显性遗传性多囊肾病上皮细胞的协同抗增殖作用。

Synergistic Antiproliferative Effects of All-Trans Retinoic Acid and Paclitaxel on Autosomal Dominant Polycystic Kidney Disease Epithelial Cells.

机构信息

Department of Life Science, Gachon University, Seongnam, Gyeonggi-Do 13120, Republic of Korea.

Department of Internal Medicine, Seoul National University College of Medicine, Seoul, Republic of Korea.

出版信息

Biomed Res Int. 2021 Oct 6;2021:1242916. doi: 10.1155/2021/1242916. eCollection 2021.

DOI:10.1155/2021/1242916
PMID:34660779
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8514275/
Abstract

Autosomal dominant polycystic kidney disease (ADPKD) is a genetic disorder characterized by uncontrollable epithelial cell growth, cyst formation, and kidney malfunction. In the present study, we investigated the antiproliferative effects of the treatment with the combination of paclitaxel (PAC) and all-trans retinoic acid (ATRA) on ADPKD epithelial cells. Our results show that the combined treatment with 1 nM PAC and 10 nM ATRA significantly suppressed ADPKD cell proliferation (20%), while the treatment with ATRA or PAC alone had no such effect. Treatment with PAC and ATRA induced cell cycle arrest at the G2/M phase and apoptosis by upregulating p53 and caspase-8 expression and increased the intracellular calcium (Ca) level possibly by enhancing Ca uptake via plasma membrane channels. In addition, this treatment suppressed extracellular signal-regulated kinase signaling possibly through mitogen-activated protein kinase phosphatase-1 activation. Thus, the combination of PAC and ATRA can be explored as a potential treatment regimen for ADPKD.

摘要

常染色体显性多囊肾病 (ADPKD) 是一种遗传性疾病，其特征为上皮细胞生长失控、囊肿形成和肾功能障碍。在本研究中，我们研究了紫杉醇 (PAC) 和全反式视黄酸 (ATRA) 联合治疗对 ADPKD 上皮细胞的抗增殖作用。我们的结果表明，1 nM PAC 和 10 nM ATRA 的联合治疗可显著抑制 ADPKD 细胞增殖（20%），而单独使用 ATRA 或 PAC 则没有这种作用。PAC 和 ATRA 的治疗通过上调 p53 和 caspase-8 的表达将细胞周期阻滞在 G2/M 期并诱导细胞凋亡，并通过增强通过质膜通道的钙摄取来增加细胞内钙 (Ca) 水平。此外，这种治疗可能通过激活丝裂原活化蛋白激酶磷酸酶-1 来抑制细胞外信号调节激酶信号。因此，PAC 和 ATRA 的联合治疗可作为 ADPKD 的一种潜在治疗方案进行探索。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/b866328c093c/BMRI2021-1242916.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/16752a7cce58/BMRI2021-1242916.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/81fae86ab461/BMRI2021-1242916.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/e0792a5bdff5/BMRI2021-1242916.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/ac10182e4df5/BMRI2021-1242916.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/dcf97fb3f5ef/BMRI2021-1242916.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/b866328c093c/BMRI2021-1242916.006.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/16752a7cce58/BMRI2021-1242916.001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/81fae86ab461/BMRI2021-1242916.002.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/e0792a5bdff5/BMRI2021-1242916.003.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/ac10182e4df5/BMRI2021-1242916.004.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/dcf97fb3f5ef/BMRI2021-1242916.005.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/a027/8514275/b866328c093c/BMRI2021-1242916.006.jpg

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引用本文的文献

[1]
ROS-responsive MSC-derived Exosome Mimetics Carrying MHY1485 Alleviate Renal Ischemia Reperfusion Injury through Multiple Mechanisms.

ACS Omega. 2024-5-28

[2]
Vitamin A and retinoid signaling in the kidneys.

Pharmacol Ther. 2023-8

[3]
Prioritized polycystic kidney disease drug targets and repurposing candidates from pre-cystic and cystic mouse Pkd2 model gene expression reversion.

Mol Med. 2023-5-22

本文引用的文献

[1]
Paclitaxel inhibits proliferation and invasion and promotes apoptosis of breast cancer cells by blocking activation of the PI3K/AKT signaling pathway.

Adv Clin Exp Med. 2020-11

[2]
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Cell Signal. 2020-3

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Hum Mol Genet. 2020-1-1

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Paclitaxel suppresses proliferation and induces apoptosis through regulation of ROS and the AKT/MAPK signaling pathway in canine mammary gland tumor cells.

Mol Med Rep. 2018-4-11

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Autosomal dominant polycystic kidney disease: recent advances in clinical management.

F1000Res. 2016-8-18

[6]
The regulation of oncogenic Ras/ERK signalling by dual-specificity mitogen activated protein kinase phosphatases (MKPs).

Semin Cell Dev Biol. 2016-2

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Biochem Biophys Res Commun. 2015-4-24

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CaMKII protects MKP-1 from proteasome degradation in endothelial cells.

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J Clin Invest. 2014-6-2

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