2. Academic Validation
  3. Liensinine inhibits progression of intrahepatic cholangiocarcinoma by regulating TGF-β1 /P-smad3 signaling through HIF-1a

Liensinine inhibits progression of intrahepatic cholangiocarcinoma by regulating TGF-β1 /P-smad3 signaling through HIF-1a

  • Mol Carcinog. 2024 Jan 30. doi: 10.1002/mc.23687.
Xuewen Zhu 1 2,  Wenming Bao 1 2,  Xiaozai Xie 1 2,  Bo Chen 1 2,  Rizhao Li 1 2,  Jungang Zhao 1 2,  Lijun Wu 1 2,  Zhengping Yu 1 2,  Shi Li 3,  Qiandong Zhu 1 2,  Gang Chen 1 2 4,  Jiacheng Li 1 2
Affiliations

Affiliations

  • 1 Department of Hepatobiliary Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 2 Key Laboratory of Diagnosis and Treatment of Severe Hepato-Pancreatic Diseases of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 3 Department of Urology Surgery, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
  • 4 Hepatobiliary Pancreatic Tumor Bioengineering Cross International Joint Laboratory of Zhejiang Province, The First Affiliated Hospital of Wenzhou Medical University, Wenzhou, China.
PMID: 38289159 DOI: 10.1002/mc.23687
Abstract

Intrahepatic cholangiocarcinoma (ICC) is a high-grade malignant digestive system tumor with an insidious onset and unfavorable prognosis. Liensinine, a small molecule derived from Plants, has been proven to have significant tumor suppressor activity in other cancers. However, there are no reports on whether liensinine can inhibit the proliferation or metastasis of ICC. This study aimed to explore the tumor-suppressive activity of liensinine in ICC and its underlying mechanisms. The phenotypic changes in ICC cells were monitored in vitro using cell function tests. Western blot and immunofluorescence analyses verified the efficacy of liensinine. Tumor-bearing nude mice were used to explore the effect of liensinine on tumors and its toxicity and side effects in vivo. Liensinine suppressed ICC cell proliferation and arrested the cell cycle at the G1 phase. The epithelial-mesenchymal transition (EMT) of ICC cells was also inhibited, thereby restraining their invasion and migration of tumor cells. In addition, this study found that the potential mechanism of liensinine inhibiting EMT may be via suppression of the TGF-β1/P-smad3 signaling pathway through hypoxia-inducible factor 1 alpha (HIF-1a). In vivo experiments showed that liensinine inhibited the growth of Hucc-T1 transplanted tumors in nude mice. Liensinine restrained the proliferation of ICC cells and suppressed EMT in ICC via the HIF-1a-mediated TGF-β1/P-smad3 signaling pathway.

Keywords

HIF-1a; cholangiocarcinoma; epithelial-mesenchymal transition; liensinine.

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