Cisplatin and PI3kinase inhibition decrease invasion and migration of human ovarian carcinoma cells and regulate...

Area of Science:

• Oncology
• Molecular Biology
• Biochemistry

Background:

• The phosphoinositide 3-kinase (PI3K)/Akt/mammalian target of rapamycin (mTOR) pathway is a key regulator of cell growth and survival.
• Aberrant PI3K/Akt/mTOR signaling is implicated in various cancers, including ovarian cancer.
• Targeting this pathway represents a promising therapeutic strategy for ovarian cancer.

Purpose of the Study:

• To investigate the effects of cisplatin and the PI3K inhibitor LY294002 on ovarian cancer cell invasion and migration.
• To examine the impact of these treatments on the expression of matrix metalloproteinases (MMPs) and their inhibitors.

Main Methods:

• Utilized three human ovarian cancer cell lines (SKOV3, OVCAR5, IGROV1).
• Treated cells with cisplatin, LY294002, or a combination of both drugs.
• Assessed cell invasion and migration using Matrigel and PET membrane assays.
• Quantified MMP and TIMP expression via Western Blotting and gel zymography.

Main Results:

• Cisplatin, LY294002, and their combination significantly reduced ovarian cancer cell invasion and migration.
• Treatments led to a marked decrease in activated matrix metalloproteinase-2 (MMP2) levels in SKOV3 cells.
• Expression of tissue inhibitor of metalloproteinase-1 (TIMP1) and TIMP2 was significantly downregulated by the treatments, particularly the combination therapy.
• Matrix metalloproteinase MT1-MMP expression remained unchanged.

Conclusions:

• Inhibition of the PI3K/Akt/mTOR pathway, combined with cisplatin, effectively reduces ovarian cancer cell motility.
• The observed anti-motility effects are associated with the downregulation of activated MMP2, TIMP1, and TIMP2.
• These findings support the therapeutic potential of targeting the PI3K/Akt/mTOR pathway in ovarian cancer treatment.