Six2 regulates the malignant progression and 5-FU resistance of hepatocellular carcinoma through the PI3K/AKT/mTOR pathway and DNMT1/E-cadherin methylation mechanism
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View abstract on PubMed
Summary
This summary is machine-generated.Six2 overexpression promotes hepatocellular carcinoma (HCC) progression and 5-fluorouracil (5-FU) resistance by affecting cell viability, invasion, and E-cadherin methylation. Targeting Six2 may enhance HCC chemotherapy sensitivity.
Area Of Science
- Oncology
- Molecular Biology
- Cancer Research
Background
- Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide.
- Therapeutic resistance to chemotherapy, such as 5-fluorouracil (5-FU), is a major challenge in HCC treatment.
- The molecular mechanisms underlying HCC progression and drug resistance require further elucidation.
Purpose Of The Study
- To investigate the role of Six2 in hepatocellular carcinoma (HCC) progression.
- To determine the involvement of Six2 in 5-fluorouracil (5-FU) resistance in HCC.
- To explore the molecular pathways regulated by Six2 in HCC, including DNMT1, E-cadherin, and PI3K/AKT/mTOR signaling.
Main Methods
- Utilized Hep3B and Huh7 HCC cell lines for experimental analysis.
- Assessed the impact of Six2 overexpression and knockdown on cell viability, proliferation, apoptosis, and invasion.
- Quantified DNMT1 levels, E-cadherin expression, and E-cadherin promoter methylation.
- Analyzed the activation status of the PI3K/AKT/mTOR signaling pathway.
Main Results
- Six2 overexpression significantly enhanced HCC cell viability, proliferation, and invasion while reducing apoptosis.
- Overexpression of Six2 led to increased DNMT1 levels, decreased E-cadherin expression, and heightened E-cadherin promoter methylation, correlating with 5-FU resistance.
- Six2 knockdown sensitized HCC cells to 5-FU and attenuated PI3K/AKT/mTOR pathway activation.
Conclusions
- Six2 plays a critical role in promoting HCC cell proliferation, invasion, and resistance to 5-FU chemotherapy.
- Six2 influences 5-FU resistance through modulation of DNMT1, E-cadherin methylation, and the PI3K/AKT/mTOR pathway.
- Targeting Six2 presents a potential therapeutic strategy to overcome chemotherapy resistance in HCC.
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