Department of Hepatobiliary and Pancreatic Surgery, The First Hospital of Jiaxing, Affiliated Hospital of Jiaxing University, No.1882 South Zhong Huan Road, Jiaxing City, Zhejiang Province, 314001, China.
Appl Biochem Biotechnol. 2024 Jan;196(1):1-17. doi: 10.1007/s12010-023-04500-2. Epub 2023 Apr 25.
Asperulosidic acid (ASPA) is a plant-extracted iridoid terpenoid with tumor-suppressive and anti-inflammatory properties. At present, the antitumor function of ASPA and its related mechanisms in hepatocellular carcinoma (HCC) cells were explored. Human normal hepatocytes HL-7702 and HCC cells (Huh7 and HCCLM3) were treated with varying concentrations (0 to 200 μg/mL) of ASPA. Cell viability, proliferation, apoptosis, migration, and invasion were checked. The expression of proteins was detected by Western blot. Furthermore, the effect of ASPA (100 μg/mL) on the sensitivity of HCC cells to chemotherapeutic agents, including doxorubicin and cisplatin, was evaluated. A subcutaneous xenografted tumor model was set up in nude mice, and the antitumor effects of ASPA were evaluated. ASPA hindered HCC cells' proliferation, migration, and invasion, and amplified their apoptosis and sensitivity to chemotherapeutic agents. Additionally, ASPA inactivated the MEKK1/NF-κB pathway. Overexpression of MEKK1 increased HCC proliferation, migration, and invasion and facilitated chemoresistance. ASPA treatment alleviated the carcinogenic effect mediated by MEKK1 overexpression. MEKK1 knockdown slowed down HCC progression. However, ASPA could not exert additional antitumor effects in MEKK1 knockdown cells. In vivo results displayed that ASPA substantially curbed tumor growth and inactivated the MEKK1/NF-κB pathway in mice. All over, ASPA exerts antitumor effects in HCC by suppressing the MEKK1/NF-κB pathway.
獐牙菜苦苷（ASPA）是一种从植物中提取的环烯醚萜类化合物，具有抗肿瘤和抗炎特性。目前，研究了 ASPA 及其在肝癌（HCC）细胞中的相关机制的抗肿瘤功能。用人正常肝细胞 HL-7702 和 HCC 细胞（Huh7 和 HCCLM3）用不同浓度（0 至 200μg/ml）的 ASPA 处理。检查细胞活力、增殖、凋亡、迁移和侵袭。通过 Western blot 检测蛋白质的表达。此外，评估了 ASPA（100μg/ml）对 HCC 细胞对包括阿霉素和顺铂在内的化疗药物的敏感性的影响。在裸鼠中建立皮下异种移植肿瘤模型，评估 ASPA 的抗肿瘤作用。ASPA 抑制 HCC 细胞的增殖、迁移和侵袭，并增强其对化疗药物的敏感性和凋亡。此外，ASPA 使 MEKK1/NF-κB 通路失活。MEKK1 的过表达增加了 HCC 的增殖、迁移和侵袭，并促进了耐药性。ASPA 治疗减轻了 MEKK1 过表达介导的致癌作用。MEKK1 敲低减缓了 HCC 的进展。然而，ASPA 不能在 MEKK1 敲低细胞中发挥额外的抗肿瘤作用。体内结果显示，ASPA 可显著抑制肿瘤生长并使小鼠中的 MEKK1/NF-κB 通路失活。总之，ASPA 通过抑制 MEKK1/NF-κB 通路在 HCC 中发挥抗肿瘤作用。
