Institute of Traditional Medicine, National Yang Ming Chiao Tung University, Taipei, Taiwan.
Cancer Progression Research Center, National Yang Ming Chiao Tung University, Taipei, Taiwan.
J Ethnopharmacol. 2023 Dec 5;317:116834. doi: 10.1016/j.jep.2023.116834. Epub 2023 Jun 22.
Kuan-Sin-Yin (KSY) is a traditional Chinese medical decoction, designed based on the classic Si-Jun-Zi-Tang decoction and used clinically to improve the synergic effects of energy promotion, liver function and cancer related symptom and quality of life. However, the anti-hepatocellular carcinoma (HCC) function of KSY is unclear.
This study aimed to investigate the anti-mobility activity of KSY on HCC cells and elucidate its molecular mechanism.
Two malignancy hepatocellular carcinoma cells, Mahlavu and SK-Hep-1, were used for the test of cell proliferation via alarm blue assay. The wound healing and Transwell assays were used to determine the anti-mobility activity of KSY in HCC cells. Cell morphology was analyzed via confocal microscopy. The genomic profile of KSY-treated HCC cells was analyzed by microarray. The potential signaling pathways and bio-functions of KSY-mediated genes were analyzed by ingenuity pathway analysis (IPA). Reverse transcription-quantitative polymerase chain reaction (RT-qPCR) was used to detect the messenger RNA (mRNA) level of indicated gene.
KSY did not affect cell viability of HCC cells but significantly inhibited cell migration and invasion in those HCC Mahlavu and SK-Hep-1 cells. In parallel, KSY induced changes in morphology of HCC cells via re-modulating actin cytoskeleton. KSY upregulated 1270 genes but reduced 1534 genes in Mahlavu cells. KSY regulated various gene networks which controlled cell migration, invasion and movement. Specifically, KSY reduced expression of chemokine (C-C motif) ligand 2 (CCL2), which is correlated to cell mobility, and concomitantly downregulated mRNA levels of phosphoinositide-3-kinase regulatory subunit 3 (PIK3R3) and CEA cell adhesion molecule 1 (CEACAM1).
These findings indicated that regulation of CCL2-mediated PIK3R3 and CEACAM1 may be involved in KSY inhibited cell mobility. Moreover, KSY may be a potential a Chinese decoction for reducing cell mobility.
宽胸饮（KSY）是一种中药方剂，基于经典的四君子汤设计，临床上用于提高能量促进、肝功能和癌症相关症状及生活质量的协同作用。然而，KSY 的抗肝癌（HCC）功能尚不清楚。
本研究旨在探讨 KSY 对肝癌细胞迁移的抑制作用及其分子机制。
选用恶性肝癌细胞 Mahlavu 和 SK-Hep-1 进行警报蓝法细胞增殖试验，划痕愈合和 Transwell 试验测定 KSY 对 HCC 细胞迁移的抑制作用，共聚焦显微镜观察细胞形态，微阵列分析 KSY 处理 HCC 细胞的基因组谱，通过 IPA 分析 KSY 介导基因的潜在信号通路和生物功能，逆转录定量聚合酶链反应（RT-qPCR）检测指定基因的信使 RNA（mRNA）水平。
KSY 不影响 HCC 细胞的活力，但显著抑制 HCC Mahlavu 和 SK-Hep-1 细胞的迁移和侵袭。同时，KSY 通过重新调节肌动蛋白细胞骨架使 HCC 细胞形态发生变化。KSY 在 Mahlavu 细胞中上调 1270 个基因，下调 1534 个基因。KSY 调节了各种控制细胞迁移、侵袭和运动的基因网络。具体来说，KSY 降低了趋化因子（C-C 基序）配体 2（CCL2）的表达，与细胞迁移有关，同时下调了磷酸肌醇-3-激酶调节亚基 3（PIK3R3）和癌胚抗原细胞粘附分子 1（CEACAM1）的 mRNA 水平。
这些发现表明，CCL2 介导的 PIK3R3 和 CEACAM1 的调节可能参与了 KSY 抑制细胞迁移的过程。此外，KSY 可能是一种潜在的减少细胞迁移的中药方剂。
