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