Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, 68 100, Greece; Postgraduate Program in Hepatobiliary and Pancreatic Surgery, 2nd Department of Surgery, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, 68 100, Greece.
Laboratory of Experimental Surgery and Surgical Research, Faculty of Medicine, Democritus University of Thrace, Alexandroupolis, 68 100, Greece.
Mutat Res Genet Toxicol Environ Mutagen. 2021 Jun;866:503352. doi: 10.1016/j.mrgentox.2021.503352. Epub 2021 Mar 24.
The potential of apigenin (APG) to enhance cisplatin's (CDDP) chemotherapeutic efficacy was investigated in HepG2, Hep3B, and Huh7 liver cancer cell lines. The presence of 20 μM APG sensitized all cell lines to CDDP treatment (degree of sensitization based on the MTT assay: HepG2>Huh7>Hep3B). As reflected by sister chromatid exchange levels, the degree of genetic instability as well as DNA repair by homologous recombination differed among cell lines. CDDP and 20 μM APG cotreatment exhibited a synergistic genotoxic effect on Hep3B cells and a less than additive effect on HepG2 and Huh7 cells. Cell cycle delays were noticed during the first mitotic division in Hep3B and Huh7 cells and the second mitotic division in HepG2 cells. CDDP and CDDP + APG treatments reduced the clonogenic capacity of all cell lines; however, there was a discordance in drug sensitivity compared with the MMT assay. Furthermore, a senescence-like phenotype was induced, especially in Hep3B and Huh7 cells. Unlike CDDP monotherapy, the combined treatment exhibited a significant anti-invasive and anti-migratory action in all cancer cell lines. The fact that the three liver cancer cell lines responded differently, yet positively, to CDDP + APG cotreatment could be attributed to variations they present in gene expression. Complex mechanisms seem to influence cellular responses and cell fate.
研究了芹菜素 (APG) 增强顺铂 (CDDP) 化疗疗效的潜力，在 HepG2、Hep3B 和 Huh7 肝癌细胞系中进行了研究。存在 20 μM APG 使所有细胞系对 CDDP 处理敏感（基于 MTT 测定的敏感程度：HepG2>Huh7>Hep3B）。反映姐妹染色单体交换水平，遗传不稳定性程度以及同源重组修复在细胞系之间存在差异。CDDP 和 20 μM APG 共处理对 Hep3B 细胞表现出协同遗传毒性作用，对 HepG2 和 Huh7 细胞表现出低于相加的作用。在 Hep3B 和 Huh7 细胞的第一次有丝分裂分裂和 HepG2 细胞的第二次有丝分裂分裂过程中观察到细胞周期延迟。CDDP 和 CDDP+APG 处理降低了所有细胞系的集落形成能力；然而，与 MMT 测定相比，药物敏感性存在差异。此外，诱导了衰老样表型，尤其是在 Hep3B 和 Huh7 细胞中。与 CDDP 单药治疗不同，联合治疗在所有癌细胞系中均表现出显著的抗侵袭和抗迁移作用。三种肝癌细胞系对 CDDP+APG 共处理的反应不同，但呈阳性，这可能归因于它们在基因表达方面的差异。复杂的机制似乎影响细胞反应和细胞命运。
