Purpose: To investigate the influence of carboplatin on the proliferation and apoptosis of ovarian cancer cells through mTOR/P70S6K signaling pathway.
Methods: The mRNA and protein expressions were detected via Western blotting and RT-PCR to study whether the mTOR/p70S6K signaling pathway was activated in OVCAR-3 and Caov-3 ovarian cancer cell lines. After cells were treated with different concentrations of carboplatin, the mRNA and protein expressions of mTOR, p70S6K and 4E-BP1 were detected via RT-PCR and Western blotting. OVCAR-3 cells were treated with 20 and 50 μM carboplatin for 4 hrs, and then apoptosis was analyzed and assessed. OVCAR-3 cells were treated with different concentrations of carboplatin (20, 50, 100, 150 and 200 μM) for 24 and 48 hrs, respectively.
Results: The mTOR signaling pathway was activated in OVCAR-3 and Caov-3 ovarian cancer cell lines. The mRNA level of mTOR in Caov-3 cells was higher, but that of p70S6K was lower. Carboplatin significantly reduced the mRNA expression of mTOR (p<0.01), whereas the mRNA expressions of p70S6K and 4E-BP1 in carboplatin-treated cells were increased in a dose-dependent manner (p<0.01). Carboplatin inhibited the mTOR protein expression in a dose-dependent manner (p<0.01). The proliferation of OVCAR-3 cells exposed to carboplatin was reduced compared with that of untreated cells (p<0.01), and the inhibitory effect of carboplatin on the proliferation of OVCAR-3 cells was time- and dose-dependent.
Conclusion: The mTOR/p70S6K pathway was activated in ovarian cancer. Carboplatin could rapidly inhibit the expression of mTOR, and the phosphorylation of its major downstream effectors p70S6K and 4E-binding protein 1 (4E-BP1) arrested cells in G0/G1 phase and induced ovarian cancer cell apoptosis.
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