Bcl-2 and CCND1/CDK4 expression levels predict the cellular effects of mTOR inhibitors in human ovarian carcinoma.
作者： D. Aguirre , P. Boya , D. Bellet , S. Faivre , F. Troalen
DOI: 10.1023/B:APPT.0000045781.46314.E2
关键词: Downregulation and upregulation 、 Ovarian carcinoma 、 Cell culture 、 Cyclin D1 、 Apoptosis 、 Cell biology 、 Biology 、 Cell cycle 、 G1 phase 、 Cancer research 、 Ovarian cancer
摘要: Molecular markers enabling the prediction of sensitivity/resistance to rapamycin may facilitate further clinical development and its derivatives as anticancer agents. In this study, several human ovarian cancer cell lines (IGROV1, OVCAR-3, A2780, SK-OV-3) were evaluated for susceptibility rapamycin-mediated growth inhibition. The differential expression profiles genes coding proteins known be involved in mTOR signaling pathway, cycle control apoptosis studied before after drug exposure by RT-PCR. cells exposed rapamycin, we observed a dose-dependent downregulation CCND1 (cyclin D1) CDK4 gene late G1 arrest. Among these lines, SK-OV-3 resistant both RAD001 sole show anti-apoptotic Bcl-2. Bcl-2/bclxL-specific antisense oligonucleotides restored sensitivity induction RAD001. These results indicate that baseline Bcl-2 therapy-induced downexpression regarded molecular follow-up cellular effects on cancer. Furthermore, strategies down regulate prove useful combination with or
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