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Notch 1 promotes cisplatin-resistant gastric cancer formation by upregulating lncRNA AK022798 expression

Qun Hang1, Ruochuan Sun, Congqiao Jiang

  • 1aDepartment of General Surgery, First Affiliated Hospital of Anhui Medical University, Hefei bDepartment of Gastric and Intestinal Surgery, First Affiliated Hospital of Bengbu Medical College, Bengbu, China.

Anti-Cancer Drugs
|March 13, 2015
PubMed

Insights

Notch 1 and long noncoding RNA (lncRNA) AK022798 promote drug resistance in gastric cancer. Targeting these may improve chemotherapy effectiveness for this common malignancy.

Area of Science:

  • Oncology
  • Molecular Biology
  • Genetics

Background:

  • Gastric cancer is a leading cause of cancer death globally.
  • Drug resistance is a major obstacle in effective gastric cancer chemotherapy.
  • Understanding the molecular mechanisms of drug resistance is crucial for developing new treatments.

Purpose of the Study:

  • To investigate the roles of Notch 1 and long noncoding RNA (lncRNA) AK022798 in the development of cisplatin resistance in gastric cancer.
  • To explore the potential of targeting Notch 1 and lncRNA AK022798 for overcoming chemotherapy resistance.

Main Methods:

  • Analysis of Notch 1 expression in cisplatin-resistant gastric cancer cell lines (SGC7901/DDP, BGC823/DDP).
  • Overexpression of Notch 1 in gastric cancer cells and assessment of drug resistance markers (MRP1, P-glycoprotein) and apoptosis.
  • Identification and functional analysis of lncRNA AK022798 using siRNA in resistant cells.
  • Evaluation of apoptosis-related proteins (caspase 3, caspase 8).

Main Results:

  • Notch 1 was significantly upregulated in cisplatin-resistant gastric cancer cells.
  • Overexpression of Notch 1 led to increased expression of MRP1 and P-glycoprotein, and reduced apoptosis.
  • Interference with lncRNA AK022798 expression decreased MRP1 and P-glycoprotein levels and enhanced apoptosis.
  • Notch 1 promotes lncRNA AK022798 expression, contributing to drug resistance.

Conclusions:

  • Notch 1 plays a critical role in promoting gastric cancer cell resistance to cisplatin, partly through upregulating lncRNA AK022798.
  • The Notch 1/lncRNA AK022798 axis is a potential therapeutic target for enhancing gastric cancer chemotherapy.
  • This study offers a novel strategy for overcoming drug resistance in gastric cancer treatment.

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