Department of Radiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China
Department of Gastroenterology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
Ann Clin Lab Sci. 2021 Jan;51(1):22-29.
All-trans retinoic acid (ATRA), a derivative of vitamin A, has been reported to exert its synergistic antitumor effect with chemotherapy in various cancer types; however, its effect in cervical cancer remains unclear. The objective of this study was to investigate the antitumor effect of ATRA with or without cisplatin and elucidate its potential mechanisms in cervical cancer cells.
Cell viability was determined by CCK-8 assay. Cell cycle and cell apoptosis were analyzed by flow cytometry. Caspase-3, cleaved caspase-3 and cell cycle-related proteins were detected by western blotting. Scratch wound-healing assay was performed to evaluate cell migration ability. The expression of CD44, a biomarker of cervical cancer stem-like cells, was determined by flow cytometry and western blotting. In addition, the activity of the Wnt signaling pathway was monitored by luciferase reporter assay and western blotting.
Compared with cisplatin treatment alone, combined use of ATRA and cisplatin significantly inhibited cell proliferation (<0.01) and migration (<0.01), and induced G0/G1 phase arrest (<0.01) and apoptosis (<0.05) in cervical cancer Hela cells. Furthermore, ATRA treatment also effectively induced differentiation of cancer stem-like cells as represented by reduced expression of CD44 and inhibited Wnt signaling pathway activity.
ATRA significantly enhanced the antitumor effect of cisplatin in cervical cancer cells, the mechanism of which might be attributed to its effect of inducing the differentiation of cancer stem-like cells.
全反式维甲酸（ATRA）是维生素 A 的衍生物，已报道其在多种癌症类型中与化疗具有协同抗肿瘤作用；然而，其在宫颈癌中的作用尚不清楚。本研究旨在探讨 ATRA 联合或不联合顺铂对宫颈癌的抗肿瘤作用，并阐明其在宫颈癌细胞中的潜在作用机制。
通过 CCK-8 法测定细胞活力。通过流式细胞术分析细胞周期和细胞凋亡。通过 Western blot 检测 caspase-3、裂解的 caspase-3 和细胞周期相关蛋白。通过划痕愈合实验评估细胞迁移能力。通过流式细胞术和 Western blot 测定 CD44（宫颈癌干细胞样细胞的标志物）的表达。此外，通过荧光素酶报告基因 assay 和 Western blot 监测 Wnt 信号通路的活性。
与单独顺铂处理相比，ATRA 联合顺铂显著抑制宫颈癌 Hela 细胞的增殖（<0.01）和迁移（<0.01），并诱导 G0/G1 期阻滞（<0.01）和凋亡（<0.05）。此外，ATRA 处理还能有效诱导肿瘤干细胞样细胞的分化，表现为 CD44 表达降低，并抑制 Wnt 信号通路的活性。
ATRA 显著增强了顺铂对宫颈癌细胞的抗肿瘤作用，其机制可能与其诱导肿瘤干细胞样细胞分化的作用有关。
