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Exosomes derived from cancer-associated fibrolasts mediated ciplatin resistance

  • 0Department of Otolaryngology, Lishui People's Hospital, Lishui, China.
Cytojournal +

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February 7, 2025

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February 7, 2025

View abstract on PubMed

Summary

This summary is machine-generated.

Cancer-associated fibroblast exosomes promote autophagy in nasopharyngeal carcinoma cells, leading to cisplatin resistance. Inhibiting exosome secretion restores sensitivity to this chemotherapy agent.

Area Of Science

  • Oncology
  • Cell Biology
  • Cancer Research

Background

  • Nasopharyngeal carcinoma (NPC) is a prevalent head and neck cancer with high metastatic potential.
  • Cisplatin-diamminedichloroplatinum (DDP) is a key chemotherapy drug for NPC, but resistance is a major clinical challenge.
  • Cancer-associated fibroblasts (CAFs) and their secreted exosomes are implicated in tumor progression and drug resistance.

Purpose Of The Study

  • To investigate the role of CAF-derived exosomes in conferring DDP resistance in NPC.
  • To elucidate the underlying molecular mechanisms, particularly the involvement of autophagy.

Main Methods

  • Establishment of an in vitro coculture system of CAFs and NPC cells.
  • Isolation and characterization of CAF-derived exosomes.
  • Assessment of autophagy markers, cell proliferation, and DDP sensitivity using Western blot, qPCR, staining, and assays.
  • Validation in an in vivo xenograft tumor model.

Main Results

  • CAF coculture and CAF-derived exosomes significantly increased NPC cell proliferation and DDP resistance.
  • Exosomes elevated autophagy markers and intensity by inhibiting the Rheb/mTORC1 axis.
  • Inhibition of exosome secretion reversed autophagy promotion and restored DDP sensitivity.

Conclusions

  • CAF-derived exosomes promote protective autophagy in NPC cells via the Rheb/mTOR pathway.
  • This exosome-mediated autophagy contributes to DDP resistance in nasopharyngeal carcinoma.

Keywords:

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