School of Pharmaceutical Sciences, Guangzhou Higher Education Mega Center, Guangzhou University of Chinese Medicine, 232, Waihuan East Road, Panyu, Guangzhou, 510000, China.
Guangdong Key Laboratory of TCM Pathogenesis and Prescriptions Realted to Heart and Spleen, Guangzhou Higher Education Mega Center, 232, Waihuan East Road, Panyu, Guangzhou, 510000, China.
J Nat Med. 2024 Jan;78(1):78-90. doi: 10.1007/s11418-023-01749-z. Epub 2023 Oct 28.
Citrinin derivatives have been found to have various pharmacological activities, such as anti-inflammatory, anti-tumor, and antioxidant effects. Dicitrinone G (DG) was a new citrinin dimer isolated from marine-derived fungus Penicillium sp. GGF 16-1-2 which has potential activity. Here, we aim to investigate whether DG has anti-pancreatic cancer activity. In xenograft tumor model, 2 × 10 BXPC-3 cells were injected into the hind flank of NU/NU nude mice by subcutaneously for 2 weeks followed by treating with DG (0.25, 0.5, 1 mg/kg) and 5-FU (30 mg/kg) for 4 weeks. Tumor volume and weight were measured, and the expression of CD31, IL-18, NLRP3, and Caspase-1 in tumor tissue were detected. In vitro, HUVECs were treated with conditioned medium (CM) derived from BXPC-3 cells, the effects of DG on angiogenesis were detected by tube formation and western blot analysis. In vivo studies showed that the tumor growth and angiogenesis were greatly suppressed. The tumor weight inhibition rates of DG and 5-FU groups were about 42.36%, 38.94%, 43.80%, and 31.88%. Furthermore, the expression of CD31 and Caspase-1 were decreased. In vitro, CM derived from BXPC-3 cells which treated with DG could inhibit the tube formation and expression of pro-angiogenic NICD in HUVECs. Our study suggests that DG could suppress angiogenesis via the NLRP3/IL-18 pathway and may have the potential to inhibit tumor development.
桔青霉素衍生物具有多种药理活性，如抗炎、抗肿瘤和抗氧化作用。二氢桔青霉素 G（DG）是一种从海洋来源的真菌青霉属 GGF 16-1-2 中分离得到的新型桔青霉素二聚体，具有潜在的活性。在这里，我们旨在研究 DG 是否具有抗胰腺癌活性。在异种移植肿瘤模型中，通过皮下将 2×10 BXPC-3 细胞注射到 NU/NU 裸鼠的后背部，2 周后用 DG（0.25、0.5、1 mg/kg）和 5-FU（30 mg/kg）处理 4 周。测量肿瘤体积和重量，并检测肿瘤组织中 CD31、IL-18、NLRP3 和 Caspase-1 的表达。在体外，用 BXPC-3 细胞的条件培养基（CM）处理 HUVECs，通过管形成和 Western blot 分析检测 DG 对血管生成的影响。体内研究表明，肿瘤生长和血管生成受到了极大的抑制。DG 和 5-FU 组的肿瘤重量抑制率约为 42.36%、38.94%、43.80%和 31.88%。此外，CD31 和 Caspase-1 的表达减少。在体外，用 DG 处理的 BXPC-3 细胞衍生的 CM 可抑制 HUVECs 中的管形成和前血管生成 NICD 的表达。我们的研究表明，DG 可通过 NLRP3/IL-18 通路抑制血管生成，并且可能具有抑制肿瘤发展的潜力。
