JoVE - Journal of Visualized Experiments
JoVE Visualize
Contact Us

Tumor-associated macrophage-derived exosome miR-194 confers cisplatin resistance in GC cells

  • 0Department of Hematology and Oncology, Wuzhong People's Hospital, Suzhou, 215000, China.
European Journal of Medical Research +

|

February 5, 2025

|

February 5, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Macrophage-derived miR-194 promotes cisplatin resistance in gastric cancer (GC) by inhibiting apoptosis via PTEN downregulation. This discovery offers new strategies for overcoming drug resistance and improving GC patient outcomes.

Area Of Science

  • Oncology
  • Cell Biology
  • Molecular Medicine

Background

  • Cisplatin is a primary chemotherapy for gastric cancer (GC), but resistance limits its effectiveness, with response rates below 20%.
  • Understanding the mechanisms of cisplatin resistance is crucial for developing strategies to improve patient outcomes.

Purpose Of The Study

  • To investigate the role of macrophage-derived exosomes in conferring cisplatin resistance in GC.
  • To identify potential therapeutic targets for reversing cisplatin resistance in GC.

Main Methods

  • Macrophages were induced and co-cultured with GC cells and cisplatin.
  • Cell viability and apoptosis were assessed using CCK-8 assays and flow cytometry.
  • Exosomal miR-194 transfer from M2 macrophages to GC cells was analyzed, and its effect on tumor growth was evaluated in a mouse model.

Main Results

  • M2 macrophages enhance GC cell cisplatin resistance primarily through exosomal miR-194.
  • miR-194 transfers from macrophages to GC cells, inhibiting apoptosis and promoting survival.
  • Macrophage-derived miR-194 downregulates PTEN, thereby enhancing cisplatin resistance.

Conclusions

  • Macrophage-derived miR-194 is a key mediator of cisplatin resistance in GC by inhibiting apoptosis via PTEN downregulation.
  • Targeting the miR-194 pathway presents a potential strategy for overcoming cisplatin resistance in GC.
  • These findings offer novel insights for improving clinical treatment strategies in gastric cancer.

Keywords:

Related Concept Videos

MicroRNAs 01:22

3.0K

MicroRNA (miRNA) are short, regulatory RNA transcribed from introns (non-coding regions of a gene) or intergenic regions (stretches of DNA present between genes). Several processing steps are required to form biologically active, mature miRNA. The initial transcript, called primary miRNA (pri-mRNA), base-pairs with itself, forming a stem-loop structure. Within the nucleus, an endonuclease enzyme, called Drosha, shortens the stem-loop structure into hairpin-shaped pre-miRNA. After the pre-miRNA...

The Tumor Microenvironment 02:17

6.5K

Every normal cell or tissue is embedded in a complex local environment called stroma, consisting of different cell types, a basal membrane, and blood vessels. As normal cells mutate and develop into cancer cells, their local environment also changes to allow cancer progression. The tumor microenvironment (TME) consists of a complex cellular matrix of stromal cells and the developing tumor. The cross-talk between cancer cells and surrounding stromal cells is critical to disrupt normal tissue...

Treatment Resistant Cancers 02:56

3.2K

Cancer is the second leading cause of death in the United States. A cancer cell is genetically unstable and hence can mutate faster. They can also modify their microenvironment and escape immune surveillance. The difficulties in treating cancer are further compounded by the emergence of rapid resistance to anticancer drugs. The most common ways to attain resistance in cancer cells include alteration in drug transport and metabolism, modification of drug target, elevated DNA damage response, or...