Department of Pharmacognosy and Ethnopharmacy, Faculty of Pharmaceutical Sciences, Usmanu Danfodiyo University Sokoto, Nigeria.
Centre for Advanced Medical Research and Training, Usmanu Danfodiyo University Sokoto, Nigeria.
Curr Drug Targets. 2023;24(11):919-928. doi: 10.2174/1389450124666230803153750.
Hepatocellular carcinoma (HCC) is associated with a high mortality rate due to early recurrence and its metastasis features. To this day, effective treatment options for metastatic HCC remain a major challenge to patient treatment. Flavokawain B (FKB) is a naturally occurring chalcone molecule capable of providing effective therapy against this life-threatening disease.
This study investigated the anti-metastatic effects of FKB on the growth and development of metastatic HCC.
HepG2 cells were used in this study and a neutral red assay was performed to determine the IC value of FKB. Cell scratch and exclusion zone assays were performed to assess the rate of cell migration and invasion. Relative mRNA levels of UCK2, and genes were quantified using RT-qPCR.
FKB inhibited the proliferation of HepG2 cells at an IC value of 28 μM after 72 h of incubation. Its cytotoxic effect was confirmed to induce apoptosis through the phase-contrast inverted microscope. Cell migration and invasion were significantly inhibited at 7, 14, and 28 μM of FKB as compared to untreated cells. The inhibition in the cell migration significantly increased with the increasing concentrations of the bioactive compound. The relative expression levels of the gene and its downstream genes, and , were significantly downregulated after 72 h exposure to FKB treatment.
Our data suggest that FKB inhibited HepG2 proliferation and further suppressed its metastasis partly by regulating the STAT3/Hif-1α/VEGF signalling pathway. FKB could be a potential alternative and viable strategy against HCC.
肝细胞癌（HCC）由于早期复发和转移特征，死亡率很高。迄今为止，转移性 HCC 的有效治疗选择仍然是患者治疗的主要挑战。 flavokawain B（FKB）是一种天然存在的查耳酮分子，能够为这种危及生命的疾病提供有效的治疗。
本研究探讨了 FKB 对转移性 HCC 生长和发展的抗转移作用。
本研究使用 HepG2 细胞，通过中性红测定法测定 FKB 的 IC 值。通过细胞划痕和排除区测定法评估细胞迁移和侵袭的速度。使用 RT-qPCR 定量测定 UCK2 和 基因的相对 mRNA 水平。
FKB 在孵育 72 小时后以 28 μM 的 IC 值抑制 HepG2 细胞的增殖。通过相差倒置显微镜证实其细胞毒性作用通过诱导细胞凋亡来实现。与未处理的细胞相比，在 7、14 和 28 μM 的 FKB 下，细胞迁移和侵袭明显受到抑制。随着生物活性化合物浓度的增加，细胞迁移的抑制作用显著增加。在暴露于 FKB 处理 72 小时后， 基因及其下游基因 和 的相对表达水平显著下调。
我们的数据表明，FKB 通过调节 STAT3/Hif-1α/VEGF 信号通路抑制 HepG2 的增殖，进一步抑制其转移。FKB 可能是 HCC 的一种潜在的替代和可行的治疗策略。
