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Per2 participates in AKT-mediated drug resistance in A549/DDP lung adenocarcinoma cells

Bo Chen1, Yaoxi Tan1, Yan Liang1

  • 1Department of Geriatrics, The First Affiliated Hospital of Nanjing Medical University, Nanjing, Jiangsu 210029, P.R. China.

Oncology Letters
|January 27, 2017
PubMed

Insights

The circadian protein Period2 (Per2) is downregulated in cisplatin-resistant lung cancer cells. Lower Per2 levels promote cell survival and drug resistance by activating the PI3K/AKT/mTOR pathway.

Area of Science:

  • Cell Biology
  • Cancer Research
  • Chronobiology

Background:

  • Period2 (Per2) is a core circadian clock protein with known tumor-suppressive roles.
  • Drug resistance remains a significant challenge in treating lung adenocarcinoma.

Purpose of the Study:

  • To investigate the role of Period2 (Per2) in cisplatin (DDP) resistance in A549 lung adenocarcinoma cells.
  • To elucidate the underlying molecular mechanisms involving the PI3K/AKT/mTOR pathway.

Main Methods:

  • Utilized Per2 knockdown and overexpression in A549/DDP cells.
  • Assessed cell proliferation (MTT assay), apoptosis (Western blot for active caspase-3), and colony formation.
  • Investigated the activation of the AKT/mechanistic target of rapamycin (mTOR) pathway via Western blot.

Main Results:

  • Per2 expression was decreased in A549/DDP cells compared to A549 cells.
  • Per2 knockdown enhanced A549/DDP cell proliferation, migration, and survival by inhibiting apoptosis.
  • Per2 knockdown led to increased activation of the phosphoinositide 3-kinase (PI3K)/AKT/mTOR pathway.
  • Per2 overexpression reduced PI3K/AKT/mTOR pathway activity and promoted apoptosis.

Conclusions:

  • Period2 (Per2) plays a crucial role in modulating cisplatin resistance in lung adenocarcinoma.
  • Per2 functions, at least partly, through the regulation of the PI3K/AKT/mTOR signaling pathway to influence drug resistance and apoptosis.
Keywords:
apoptosischemoresistancelung cancerperiod2phosphoinositide 3-kinase/AKT/mechanistic target of rapamycin

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