Department of Oncology, Clinical and Basic Research Team of TCM Prevention and Treatment of NSCLC, The Second Clinical College of Guangzhou University of Chinese Medicine, Guangdong Provincial Hospital of Chinese Medicine, Guangzhou, Guangdong, P.R. China.
Guangdong Provincial Key Laboratory of Clinical Research on Traditional Chinese Medicine Syndrome, Guangzhou, Guangdong, P.R. China.
Mol Carcinog. 2022 Apr;61(4):417-432. doi: 10.1002/mc.23389. Epub 2022 Jan 17.
Hepatocellular carcinoma (HCC) is one of the most common primary malignancies. Drug resistance has significantly prevented the clinical application of sorafenib (SF), a first-line targeted medicine for the treatment of HCC. Solamargine (SM), a natural alkaloid, has shown potential antitumor activity, but studies about antitumor effect of SM are obviously insufficient in HCC. In the present study, we found that SM significantly inhibited the growth of HCC and enhanced the anticancer effect of SF. In brief, SM significantly inhibited the growth of HepG2 and Huh-7 cells. The combination of SM and SF showed a synergistic antitumor effect. Mechanistically, SM downregulated the expression of long noncoding RNA HOTTIP and TUG1, followed by increasing the expression of miR-4726-5p. Moreover, miR-4726-5p directly bound to the 3'-UTR region of MUC1 and decreased the expression of MUC1 protein. Overexpression of MUC1 partially reversed the inhibitory effect of SM on HepG2 and Huh-7 cells viability, which suggested that MUC1 may be the key target in SM-induced growth inhibition of HCC. More importantly, the combination of SM and SF synergistically restrained the expression of MUC1 protein. Taken together, our study revealed that SM inhibited the growth of HCC and enhanced the anticancer effect of SF through HOTTIP-TUG1/miR-4726-5p/MUC1 signaling pathway. These findings will provide potential therapeutic targets and strategies for the treatment of HCC.
肝细胞癌 (HCC) 是最常见的原发性恶性肿瘤之一。耐药性显著阻碍了索拉非尼 (SF) 的临床应用，SF 是治疗 HCC 的一线靶向药物。苦参碱 (SM) 是一种天然生物碱，具有潜在的抗肿瘤活性，但关于 SM 在 HCC 中的抗肿瘤作用的研究明显不足。在本研究中，我们发现 SM 显著抑制 HCC 的生长并增强 SF 的抗癌作用。简而言之，SM 显著抑制 HepG2 和 Huh-7 细胞的生长。SM 和 SF 的联合具有协同的抗肿瘤作用。机制上，SM 下调长链非编码 RNA HOTTIP 和 TUG1 的表达，随后增加 miR-4726-5p 的表达。此外，miR-4726-5p 直接结合 MUC1 的 3'-UTR 区域并降低 MUC1 蛋白的表达。MUC1 的过表达部分逆转了 SM 对 HepG2 和 Huh-7 细胞活力的抑制作用，这表明 MUC1 可能是 SM 诱导 HCC 生长抑制的关键靶标。更重要的是，SM 和 SF 的联合协同抑制了 MUC1 蛋白的表达。总之，我们的研究表明，SM 通过 HOTTIP-TUG1/miR-4726-5p/MUC1 信号通路抑制 HCC 的生长并增强 SF 的抗癌作用。这些发现将为 HCC 的治疗提供潜在的治疗靶点和策略。
Naunyn Schmiedebergs Arch Pharmacol. 2025-7-5
Discov Oncol. 2024-11-11
Cancer Manag Res. 2020-11-2
Cancers (Basel). 2020-6-15
Biomed Pharmacother. 2020-7
Clin Epigenetics. 2020-3-2
BMC Cardiovasc Disord. 2020-2-3
Zotero 插件
