Effect of trastuzumab on the antiproliferative effects of PI3K inhibitors in HER2+ breast cancer cells with de novo resistance to trastuzumab.

e11592 Background: Despite the therapeutic success of trastuzumab, only 30% of tumors that overexpress HER2 respond. The PI3K/AKT pathway appears to be an important mechanism of resistance. It is known that HER2 receptor and PI3K pathways can be modulated by different miRNAs. The purpose of this study was to investigate the mechanisms of PI3K in resistance to trastuzumab by the evaluation of inhibitory drugs and relevant microRNAs in the context of de novo resistance. Methods: The cell line HCC1954, with de novo resistance to trastuzumab, was treated with the inhibitors BKM120 (PI3K), MK2206 (Akt1/2/3), everolimus (mTOR) and GDC-0980 (dual PI3K-mTOR) alone or in combination with trastuzumab. Cell viability was determined by the colorimetric assay MTT. The expression of miR-21, miR-221, miR-26a and mi-R30b was also evaluated after treatments by quantitative PCR. The transfection of mimetic microRNAs was performed by internalization with the no liposomal TransIT-X2TM reagent (Mirus). Differences in mean bet...