Hepatocellular carcinoma (HCC) is one of the few cancers with a continuous increase in incidence and mortality. Drug resistance is a major problem in the treatment of HCC. In this study, two sorafenib-resistant HCC cell lines and a nude mouse subcutaneously tumor model were used to explore the possible mechanisms leading to sorafenib resistance, and to investigate whether aspirin could increase the sensitivity of hepatoma cells to sorafenib. The combination of aspirin and sorafenib resulted in a synergistic antitumor effect against liver tumors both in vitro and in vivo. High glycolysis and PFKFB3 overexpression occupied a dominant position in sorafenib resistance, and can be targeted and overcome by aspirin. Aspirin plus sorafenib induced apoptosis in tumors without inducing weight loss, hepatotoxicity or inflammation. Our results suggest that aspirin overcomes sorafenib resistance and their combination may be an effective treatment approach for HCC.
Download full-text PDF |
Source |
|---|---|
| http://dx.doi.org/10.1002/ijc.31022 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
BRAF-activated ARSI suppressed EREG-mediated ferroptosis to promote BRAF (mutant) papillary thyroid carcinoma progression and sorafenib resistance.
Int J Biol Sci
January 2025
Department of Thyroid and Hernia Surgery, Shengli Clinical Medical College of Fujian Medical University, Fujian Provincial Hospital, Fuzhou University Affiliated Provincial Hospital, Fuzhou City, Fujian Province 350001, China.
Papillary thyroid carcinoma (PTC) is the most common type of thyroid cancer, and patients with the BRAF mutation often exhibit aggressive tumor behavior. Here, we identified Arylsulfatase I (ARSI) as a gene whose expression was significantly upregulated in BRAF PTC and was associated with poor prognosis. High ARSI expression correlated with advanced disease stage, BRAF mutation, and worse overall survival in PTC patients.
View Article and Find Full Text PDFTranscription factor MEF2D regulates aberrant expression of ACSL3 and enhances sorafenib resistance by inhibiting ferroptosis in HCC.
Front Pharmacol
December 2024
Qingdao Cancer Institute, The Affiliated Hospital of Qingdao University, Qingdao University, Qingdao, China.
Background: Sorafenib is a first-line treatment for hepatocellular carcinoma (HCC); however, acquired resistance often results in a poor prognosis, indicating a need for more effective therapies. Sorafenib induces cell death through an iron-dependent mechanism known as ferroptosis, which is closely associated with the onset and progression of HCC.
Methods: This study investigated the role of ACSL3 in sorafenib resistance and ferroptosis in HCC.
Sorafenib promotes Treg cell differentiation to compromise its efficacy via VEGFR/AKT/Foxo1 signaling in hepatocellular carcinoma.
Cell Mol Gastroenterol Hepatol
December 2024
Department of Medical Oncology, Cancer Center of Zhejiang University, Sir Run Run Shaw Hospital, Medical School of Zhejiang University, Hangzhou, Zhejiang 310020, China.
Unlabelled: Our study revealed that sorafenib (Sora) induced the formation of an immunosuppressive tumor microenvironment in hepatocellular carcinoma (HCC) by promoting the differentiation of regulatory T (Treg) cells through VEGFR/AKT/Foxo1 signaling, leading to compromised Sora efficacy. Importantly, combination treatment with an anti-CD25 antibody or the Foxo1 inhibitor AS1842856 inhibited Treg cell differentiation and increased the therapeutic efficacy of Sora in HCC.
Background & Aims: Sora is the first-line drug for advanced HCC.
N6-methyladenosine-modified long non-coding RNA promotes stemness and sorafenib resistance in hepatocellular carcinoma by upregulating SHOX2 expression.
World J Gastroenterol
December 2024
Department of Gastroenterology and Hepatology, The First Medical Center, Chinese People's Liberation Army General Hospital, Beijing 100853, China.
Background: Hepatocellular carcinoma (HCC) is a prevalent and aggressive tumor. Sorafenib is the first-line treatment for patients with advanced HCC, but resistance to sorafenib has become a significant challenge in this therapy. Cancer stem cells play a crucial role in sorafenib resistance in HCC.
View Article and Find Full Text PDFRoles and Mechanisms of Ferroptosis in Sorafenib Resistance for Hepatocellular Carcinoma.
J Hepatocell Carcinoma
December 2024
Guangxi Key Laboratory of Environmental Exposomics and Entire Lifecycle Health, Guilin Medical University, Guilin, 541199, People's Republic of China.
Hepatocellular carcinoma (HCC) is the most prevalent malignant tumor, characterized by a poor prognosis. In recent decades, both the incidence and mortality rates of HCC have risen sharply. Sorafenib has emerged as the first conventional drug approved by the US Food and Drug Administration for first-line treatment in advanced HCC patients due to its favorable safety profile.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!