Department of Hepatobiliary Surgery, Affiliated Drum Tower Hospital of Nanjing University Medical School, Nanjing, Jiangsu Province, China.
Department of Hepatobiliary Surgery, Nanjing Drum Tower Hospital Clinical College of Nanjing Medical University, Nanjing, Jiangsu Province, China.
Braz J Med Biol Res. 2020 Mar 31;53(4):e8882. doi: 10.1590/1414-431X20198882. eCollection 2020.
Hepatocellular carcinoma (HCC) is one of the most common primary malignant tumors of the liver worldwide. Liver resection and transplantation are currently the only effective treatments; however, recurrence and metastasis rates are still high. Previous studies have shown that the epithelial-mesenchymal transition (EMT) is a key step in HCC invasion and metastasis. Inhibition of EMT has become a new therapeutic strategy for tumors. Recently, puerarin, a well-characterized component of traditional Chinese medicine, has been isolated from Pueraria radix and exerts positive effects on many diseases, particularly cancers. In this study, CCK-8, EdU immunofluorescence, colony formation, wound healing, and migration assays were used to detect the effects of puerarin on HCC cells. We further analyzed the relationship between puerarin and miR-21/PTEN/EMT markers in HCC cell lines. Our results showed that HCC cell proliferation, migration, invasion, tumor formation, and metastasis were reduced by puerarin in vitro and in vivo. Additionally, puerarin inhibited the EMT process of HCC by affecting the expression of Slug and Snail. Moreover, oncogenic miR-21 was inhibited by puerarin, coupled with an increase in the tumor suppressor gene PTEN. Increasing miR-21 expression or decreasing PTEN expression reversed the inhibition effects of puerarin in HCC. These data confirmed that puerarin affects HCC through the miR-21/PTEN/EMT regulatory axis. Overall, puerarin may represent a chemopreventive and/or chemotherapeutic agent for HCC treatment.
肝细胞癌（HCC）是全球最常见的原发性肝脏恶性肿瘤之一。肝切除术和肝移植是目前唯一有效的治疗方法，但复发和转移率仍然很高。先前的研究表明，上皮-间充质转化（EMT）是 HCC 侵袭和转移的关键步骤。抑制 EMT 已成为肿瘤的一种新的治疗策略。最近，葛根素作为一种中药的典型成分，已从葛根中分离出来，并对许多疾病，特别是癌症，发挥积极作用。在这项研究中，使用 CCK-8、EdU 免疫荧光、集落形成、划痕愈合和迁移实验来检测葛根素对 HCC 细胞的影响。我们进一步分析了葛根素与 HCC 细胞系中 miR-21/PTEN/EMT 标志物之间的关系。结果表明，葛根素在体外和体内均可降低 HCC 细胞的增殖、迁移、侵袭、肿瘤形成和转移。此外，葛根素通过影响 Slug 和 Snail 的表达来抑制 HCC 的 EMT 过程。此外，致癌 miR-21 被葛根素抑制，同时肿瘤抑制基因 PTEN 增加。增加 miR-21 的表达或降低 PTEN 的表达可逆转葛根素对 HCC 的抑制作用。这些数据证实，葛根素通过 miR-21/PTEN/EMT 调节轴影响 HCC。总之，葛根素可能代表 HCC 治疗的一种化学预防和/或化学治疗剂。
