Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 2024 Jan 6;24(1):5.
doi: 10.1007/s10142-024-01286-2.

Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma

Wenhua Wu  1 , Yaping Li  2 , Xiaokang Wu  3 , Junrong Liang  4 , Weiming You  5   6 , Xinyuan He  2 , Qinhui Feng  7 , Ting Li  2 , Xiaoli Jia  8
Affiliations

Carnosic acid nanocluster-based framework combined with PD-1 inhibitors impeded tumorigenesis and enhanced immunotherapy in hepatocellular carcinoma

Wenhua Wu et al. Funct Integr Genomics. .

Retraction in

Abstract

Clinically, the immune checkpoint inhibitor anti-PD-1 antibody has shown a certain effect in the treatment of hepatocellular carcinoma (HCC), which is limited to a small number of patients with HCC. This study aims to reveal whether carnosic acid nanocluster-based framework (CA-NBF) has a sensitization effect on anti-PD-1 antibody in the treatment of HCC at the cellular and animal levels. MHCC97H cells were treated with CA-NBF, anti-PD-1 and their combination. The effects of CA-NBF and anti-PD-1 on cell proliferation, cell cycle, apoptosis, invasion, and migration were evaluated by MTT assay, flow cytometry, and scratch test. The effects of CA-NBF and anti-PD-1 on Wnt/β-catenin signaling pathway in MHCC97H cells were detected. A BALB/C nude mouse model of hepatocellular carcinoma was established, and the tumor growth was observed at different time points. The expression of cytotoxic T lymphocyte and helper T lymphocyte markers CD8 and CD4 in tumor tissues was detected by immunohistochemistry. Western blotting was used to detect the Wnt/β-catenin signaling pathway proteins (Wnt-3a, β-catenin, and GSK-3β) level in tumor tissues after CA-NBF and anti-PD-1 treatment. CA-NBF activity was significantly higher than CA, which could prominently reduce the proliferation, migration and invasion of MHCC97H cells and enhance apoptosis by inactivating Wnt/β-catenin signaling pathway. CA-NBF combined with anti-PD-1 antibody further enhanced cell proliferation, migration, invasion and pro-apoptosis but had no significant effect on Wnt/β-catenin signaling pathway. CA-NBF in vivo improved the tumor response to PD1 immune checkpoint blockade in HCC, manifested by reducing tumor size and weight, promoting CD4 and CD8 expression. CA-NBF combined with anti-PD-1 have stronger immunomodulatory and anticancer effects without increasing biological toxicity.

Keywords: Carnosic acid; Hepatocellular carcinoma; Immunotherapy; Nanocluster; PD-1.

PubMed Disclaimer

References

    1. Allen TM (2002) Ligand-targeted therapeutics in anticancer therapy. Nat Rev Cancer 2(10):750–763. https://doi.org/10.1038/nrc903 - DOI - PubMed
    1. Barni MV, Carlini MJ, Cafferata EG, Puricelli L, Moreno S (2012) Carnosic acid inhibits the proliferation and migration capacity of human colorectal cancer cells. Oncol Rep 27(4):1041–1048. https://doi.org/10.3892/or.2012.1630 - DOI - PubMed - PMC
    1. Cheng F, Wang L, Yi S, Liu G (2022) Long non-coding RNA SNHG1/microRNA-195-5p/Yes-associated protein axis affects the proliferation and metastasis of gastric cancer via the Hippo signaling pathway. Funct Integr Genomics 22(5):1043–1055. https://doi.org/10.1007/s10142-022-00876-2 - DOI - PubMed
    1. Chiew Woon L, Joycelyn Jie Xin L, Su Pin C (2020) Nivolumab for the treatment of hepatocellular carcinoma. Expert Opin Biol Ther 20(7):687–693. https://doi.org/10.1080/14712598.2020.1749593 - DOI - PubMed
    1. Deng R, Zuo C, Li Y, Xue B, Xun Z, Guo Y et al (2020) The innate immune effector ISG12a promotes cancer immunity by suppressing the canonical Wnt/β-catenin signaling pathway. Cell Mol Immunol 17(11):1163–1179. https://doi.org/10.1038/s41423-020-00549-9 - DOI - PubMed - PMC

Publication types

LinkOut - more resources