Morphine promotes non-small cell lung cancer progression by downregulating E-cadherin via the PI3K/AKT/mTOR pathway

  • 0Postgraduate Training Base Alliance of Wenzhou Medical University (Zhejiang Cancer Hospital), Hangzhou, 310022, Zhejiang, China.

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Summary

This summary is machine-generated.

Morphine promotes non-small cell lung cancer (NSCLC) progression by increasing cell proliferation, migration, and invasion. It activates the PI3K/AKT/mTOR pathway and reduces E-cadherin, driving tumor growth.

Area Of Science

  • Oncology
  • Pharmacology
  • Molecular Biology

Background

  • Morphine's impact on lung cancer survival is debated, with unclear molecular mechanisms.
  • Understanding morphine's effects on non-small cell lung cancer (NSCLC) is crucial.

Purpose Of The Study

  • To investigate the molecular mechanisms of morphine's influence on NSCLC malignancy.
  • To explore how morphine affects cancer cell proliferation, migration, and invasion.

Main Methods

  • Assessed cell proliferation, migration, and invasion in A549 and Lewis lung cancer (LLC) cells.
  • Evaluated E-cadherin expression via immunofluorescence and immunohistochemistry.
  • Analyzed protein levels of E-cadherin, PI3K/AKT/mTOR pathway components via Western blot.
  • Investigated in vivo effects using a xenograft mouse model with naloxone as an antagonist.

Main Results

  • Morphine (10 µM) significantly increased proliferation, migration, and invasion in A549 and LLC cells.
  • Morphine reduced E-cadherin expression and increased PI3K, AKT, and mTOR phosphorylation.
  • In vivo, morphine (1.5 mg/kg) promoted tumor growth and reduced E-cadherin, effects reversed by naloxone (0.1 mg/kg).

Conclusions

  • Morphine stimulates NSCLC proliferation and xenograft tumor growth.
  • Morphine likely activates the PI3K/AKT/mTOR pathway and inhibits E-cadherin, promoting lung cancer progression.
  • Targeting the mu-opioid receptor (MOR) may be a therapeutic strategy.

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