Department of Pharmacy, Shenzhen University General Hospital, Shenzhen University Clinical Medical Academy, Shenzhen University, Shenzhen, Guangdong, China.
Department of Hepatobiliary Surgery, Peking University Shenzhen Hospital, Shenzhen, Guangdong, China.
Front Immunol. 2023 Jul 28;14:1223650. doi: 10.3389/fimmu.2023.1223650. eCollection 2023.
Pancreatic ductal adenocarcinoma (PDAC) is one of the most malignant and lethal human cancers in the world due to its high metastatic potential, and patients with PDAC have a poor prognosis, yet quite little is understood regarding the underlying biological mechanisms of its high metastatic capacity. Baicalein has a dramatic anti-tumor function in the treatment of different types of cancer. However, the therapeutic effects of baicalein on human PDAC and its mechanisms of action have not been extensively understood. In order to explore the biological characteristic, molecular mechanisms, and potential clinical value of baicalein in inhibiting the metastatic capacity of PDAC. We performed several , , and studies. We first examined the potential regulation of baicalein in the metastatic capacity of PDAC cells. We showed that baicalein could dramatically suppress liver metastasis of PDAC cells with highly metastatic potential in mice model. The high-throughput sequencing analysis was employed to explore the biological roles of baicalein in PDAC cells. We found that baicalein might be involved in the infiltration of Cancer-Associated Fibroblasts (CAF) in PDAC. Moreover, a baicalein-related risk model and a lncRNA-related model were built by Cox analysis according to the data set of PDAC from TCGA database which suggested a clinical value of baicalein. Finally, we revealed a potential downstream target of baicalein in PDAC, we proposed that baicalein might contribute to the infiltration of CAF via FGFBP1. Thus, we uncovered a novel role for baicalein in regulation of PDAC liver metastasis that may contribute to its anti-cancer effect. We proposed that baicalein might suppress PDAC liver metastasis via regulation of FGFBP1-mediated CAF infiltration. Our results provide a new perspective on clinical utility of baicalein and open new avenues for the inhibition of liver-metastasis of PDAC.
胰腺导管腺癌（PDAC）是世界上最恶性和最致命的人类癌症之一，由于其高转移潜能，PDAC 患者的预后较差，但对于其高转移能力的潜在生物学机制知之甚少。黄芩素在治疗不同类型的癌症方面具有显著的抗肿瘤功能。然而，黄芩素对人 PDAC 的治疗效果及其作用机制尚未得到广泛理解。为了探讨黄芩素抑制 PDAC 转移能力的生物学特性、分子机制和潜在临床价值，我们进行了几项研究。我们首先研究了黄芩素对 PDAC 细胞转移能力的潜在调控作用。我们发现黄芩素可以显著抑制具有高转移潜能的 PDAC 细胞在小鼠模型中的肝转移。我们采用高通量测序分析来研究黄芩素在 PDAC 细胞中的生物学作用。我们发现黄芩素可能参与 PDAC 细胞中癌症相关成纤维细胞（CAF）的浸润。此外，我们根据 TCGA 数据库中 PDAC 的数据集，通过 Cox 分析构建了一个黄芩素相关风险模型和一个 lncRNA 相关模型，提示了黄芩素的临床价值。最后，我们揭示了黄芩素在 PDAC 中的一个潜在下游靶标，我们提出黄芩素可能通过 FGFBP1 促进 CAF 的浸润。因此，我们揭示了黄芩素在调节 PDAC 肝转移中的一个新作用，这可能有助于其抗癌作用。我们提出，黄芩素可能通过调节 FGFBP1 介导的 CAF 浸润来抑制 PDAC 肝转移。我们的研究结果为黄芩素的临床应用提供了一个新的视角，并为抑制 PDAC 的肝转移开辟了新的途径。
