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The mTORC2 component rictor contributes to cisplatin resistance in human ovarian cancer cells

Akechai Im-aram1, Lee Farrand, Seung-Min Bae

  • 1World Class University Biomodulation Major, Department of Agricultural Biotechnology, College of Agriculture and Life Sciences, Seoul National University, Seoul, Republic of Korea.

Plos One
|October 3, 2013
PubMed

Insights

Rictor protein is key to cisplatin resistance in ovarian cancer. Reducing rictor levels can sensitize resistant cells to chemotherapy by impacting Akt and p53 pathways.

Area of Science:

  • Oncology
  • Molecular Biology
  • Biochemistry

Background:

  • Cisplatin resistance is a major challenge in ovarian cancer treatment.
  • Akt and p53 are known factors influencing cisplatin sensitivity.
  • The role of rictor (a component of mTOR complex 2) in cisplatin resistance is not fully understood.

Purpose of the Study:

  • To investigate the role of rictor in cisplatin resistance in human ovarian cancer cells.
  • To elucidate the relationship between rictor, Akt, and p53 in the context of cisplatin resistance.

Main Methods:

  • Utilized sensitive and resistant human ovarian cancer cell lines with wild-type or compromised p53.
  • Analyzed rictor expression and its regulation by cisplatin.
  • Assessed the impact of rictor modulation on cisplatin-induced apoptosis and Akt activation.

Main Results:

  • Rictor was identified as a determinant of cisplatin resistance in chemosensitive ovarian cancer cells.
  • Cisplatin treatment led to decreased rictor levels via caspase-3 cleavage and proteasomal degradation.
  • Down-regulation of rictor sensitized chemo-resistant cells to cisplatin-induced apoptosis in a p53-dependent manner.
  • Rictor was found to suppress apoptosis and confer resistance by activating and stabilizing Akt.

Conclusions:

  • Rictor plays a significant role in conferring cisplatin resistance in ovarian cancer.
  • Targeting rictor may offer a novel therapeutic strategy for overcoming chemoresistance in ovarian cancer.
  • Findings provide a deeper understanding of the molecular mechanisms underlying cisplatin resistance.

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