Department of Hepatobiliary Surgery, Guizhou Provincial People's Hospital, Guiyang, Guizhou, China (mainland).
Med Sci Monit. 2019 Sep 7;25:6711-6718. doi: 10.12659/MSM.916635.
BACKGROUND Liver cancer is one of the most common malignancies around the world and one of the major causes of cancer related mortality. The objective of this study was to evaluate the anticancer effect of the natural compound psilostachyin-A on 5-fluorouracil-resistant human liver carcinoma cells and its effects on autophagy, cell cycle, caspase activation, and the ERK/MAPK signaling pathway. MATERIAL AND METHODS Cell Counting Kit 8 (CCK-8) assay was used to evaluate the effects on HepG2 cell viability at different doses of psilostachyin-A. Cell cycle analysis was performed using flow cytometry, and Transwell assay was used to check effects on cell invasion. Transmission electron microscopic studies were done to evaluate autophagy induced by psilostachyin-A, and the western blot method was carried out to evaluate the effects on autophagy and the ERK/MAPK signaling pathway. RESULTS CCK-8 assay revealed that the psilostachyin-A reduced the cell viability of HepG2 cancer cells in a dose dependent manner. Psilostachyin-A also reduced the colony forming potential of HepG2 cells, concentration dependently. The IC50 of psilostachyin was found to be 25 µM. The anticancer effects of psilostachyin-A were due to the induction of autophagy which was accompanied by enhancement of LC3B II expression. Psilostachyin also caused cell cycle arrest by enhancing the accumulation of HepG2 cells in the G2/M phase. Transwell assay showed that psilostachyin-A suppressed the invasion of HepG2 cells. The results also showed that psilostachyin-A could block the ERK/MAPK pathway, indicative of the cytotoxic effects of psilostachyin-A on liver cancer. CONCLUSIONS These preliminary observations suggested that psilostachyin-A might prove beneficial in the treatment of liver cancer.
肝癌是全球最常见的恶性肿瘤之一，也是癌症相关死亡的主要原因之一。本研究旨在评估天然化合物 psilostachyin-A 对氟尿嘧啶耐药人肝癌细胞的抗癌作用及其对自噬、细胞周期、半胱天冬酶激活和 ERK/MAPK 信号通路的影响。
采用细胞计数试剂盒 8（CCK-8）法评估不同剂量 psilostachyin-A 对 HepG2 细胞活力的影响。采用流式细胞术进行细胞周期分析，采用 Transwell assay 检测细胞侵袭的影响。透射电子显微镜研究用于评估 psilostachyin-A 诱导的自噬，采用 Western blot 法评估自噬和 ERK/MAPK 信号通路的影响。
CCK-8 assay 结果表明，psilostachyin-A 以剂量依赖性方式降低 HepG2 癌细胞的细胞活力。psilostachyin-A 还浓度依赖性地降低 HepG2 细胞的集落形成能力。发现 psilostachyin 的 IC50 为 25 µM。psilostachyin-A 的抗癌作用是由于诱导自噬，同时增强 LC3B II 的表达。psilostachyin 还通过增加 HepG2 细胞在 G2/M 期的积累来引起细胞周期停滞。Transwell assay 显示 psilostachyin-A 抑制 HepG2 细胞的侵袭。结果还表明，psilostachyin-A 可以阻断 ERK/MAPK 通路，表明 psilostachyin-A 对肝癌具有细胞毒性作用。
这些初步观察结果表明，psilostachyin-A 可能在治疗肝癌方面具有有益作用。
