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SDC1 promotes cisplatin resistance in hepatic carcinoma cells via PI3K-AKT pathway

Liquan Yu1, Hong Xu1, Song Zhang1

  • 1General Surgery, The Second Affiliated Hospital of Anhui Medical University, No. 678 Furong Road, Hefei, 230601, Anhui, China.

Human Cell
|April 22, 2020
PubMed

Insights

Syndecan 1 (SDC1) promotes cisplatin resistance in liver cancer by activating the PI3K/AKT pathway. Reducing SDC1 levels can re-sensitize cancer cells to this chemotherapy, offering a potential therapeutic target.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Hepatocellular carcinoma (HCC) is a major global health concern.
  • Cisplatin is a widely used chemotherapy agent, but resistance limits its efficacy.
  • The molecular mechanisms underlying cisplatin resistance in HCC require further elucidation.

Purpose of the Study:

  • To investigate the role of Syndecan 1 (SDC1) in conferring cisplatin resistance in hepatic carcinoma.
  • To explore the underlying signaling pathways involved in SDC1-mediated drug resistance.

Main Methods:

  • Cell proliferation and viability assays (direct counting, MTT).
  • Western blotting for protein quantification (SDC1, p-AKT, AKT, β-actin).
  • Real-time polymerase chain reaction for SDC1 transcript levels.
  • Immunohistochemistry for SDC1 expression in clinical HCC samples.

Main Results:

  • SDC1 was significantly upregulated in cisplatin-resistant HepG2 cells (HepG2 CR).
  • SDC1 knockdown resensitized HepG2 CR cells to cisplatin; SDC1 overexpression induced resistance in naïve cells.
  • The PI3K/AKT pathway was hyperactivated in HepG2 CR cells, and PI3K inhibition overcame resistance.
  • Aberrant SDC1 upregulation was observed in clinical HCC samples.

Conclusions:

  • SDC1 plays a crucial role in the development of cisplatin resistance in hepatocellular carcinoma.
  • The SDC1-PI3K/AKT signaling axis is a key mediator of this drug resistance.
  • Targeting SDC1 or the PI3K/AKT pathway may represent a viable strategy to overcome cisplatin resistance in HCC.
Keywords:
AKTCisplatin resistanceHepatocellular carcinomaSDC1

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