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Cystathionine β-synthase Induces Multidrug Resistance and Metastasis in Hepatocellular Carcinoma

Lupeng Wang1, Huanxiao Han1, Ya Liu1

  • 1College of Pharmacy, Joint International Research Laboratory of Food & Medicine，Henan University, Kaifeng 475004, Henan Province, China.

Current Molecular Medicine
|December 13, 2018
PubMed
Abstract

Insights

Cystathionine β-synthase (CBS) overexpression increases resistance to chemotherapy drugs like doxorubicin and sunitinib in hepatocellular carcinoma (HCC) cells. Reducing CBS levels enhances drug sensitivity in HCC, highlighting CBS as a target for overcoming drug resistance.

Area of Science:

  • Oncology
  • Biochemistry
  • Molecular Biology

Background:

  • Hepatocellular carcinoma (HCC) remains a leading cause of cancer-related mortality worldwide.
  • Drug resistance significantly limits the efficacy of chemotherapeutic treatments for HCC.
  • Identifying novel molecular targets is crucial for improving HCC treatment outcomes.

Purpose of the Study:

  • To investigate the role of Cystathionine β-synthase (CBS) in the development of drug resistance in hepatocellular carcinoma (HCC).
  • To determine the impact of CBS expression levels on the sensitivity of HCC cells to common chemotherapeutic agents.

Main Methods:

  • Cell viability assays (MTS) were used to assess drug sensitivity.
  • Doxorubicin accumulation and P-glycoprotein (P-gp) expression were quantified.
  • Hydrogen sulfide (H2S) and reactive oxygen species (ROS) levels were measured.
  • Cell migration and invasion were evaluated using scratch wound and transwell assays.
  • Protein expression was analyzed via Western blot.

Main Results:

  • High CBS expression correlated with reduced sensitivity to doxorubicin (DOX) and sunitinib in HCC cells.
  • Knockdown of CBS significantly increased HCC cell sensitivity to DOX and sunitinib.
  • CBS overexpression led to increased P-gp expression and decreased DOX accumulation.
  • CBS promoted HCC drug resistance via STAT3/Akt/Bcl-2 pathway activation, ROS inhibition, and enhanced metastasis.

Conclusions:

  • CBS overexpression confers drug resistance in hepatocellular carcinoma.
  • Targeting CBS may represent a viable strategy to overcome chemotherapy resistance in HCC.
Keywords:
Cystathionine β-synthaseDOXGSThepatocellular carcinomametastasismultidrug resistance.

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