Abstract P6-12-08: The effects of the BKM120 in combination with herceptin on HER2+ BC cells and BCSCs

Abstract

Abstract Introduction: Breast cancer stem cells (BCSCs) are suspected to be responsible for tumour recurrence, metastasis as well as chemo-resistance. Dysregulated PI3K/Akt signaling is implicated in the pathogenesis of a number of breast cancers, including the HER2+ breast cancer. This study evaluated the efficacy of BKM120 monotherapy and BKM120 plus Herceptin in treatment of normal cells and the BCSCs of the HER2+ breast cancer . Methods:The BCSCs of SK-BR-3 cells were isolated by Serum free cells suspension culture. The impacts of BKM120 monotherapy and BKM120 combined with Herceptin on normal breast cancer cells and BCSCs were assayed by MTT assay, wound-healing assay and plate clone formation assay. The mammosphere-forming efficiency (MFE) of breast cancer cells treated with BKM120 and BKM120 plus Herceptin were also calculated. The nature of the drug interaction of BKM120 and Herceptin was evaluated by using the combination index (CI) according to the method of Chou and Talalay. The impacts of BKM120 monotherapy and BKM120 combined with Herceptin in PI3K/AKT pathway on the normal cancer cells and BCSCs of SK-BR-3 were assayed by Western bloting. Results: BKM120 showed significant antiproliferative activity in the BCSCs, as well as in normal SK-BR-3 cells. After treated with BKM120, invasion abilities of SK-BR-3 cells was significantly weakened(P<0.01).The colony forming efficiency and the MFE was also decreased compared with the control (P<0.01). Additionally, the pAKT and pS6 expression levels were inhibited. The effects of BKM120 in combination with Herceptin were investigated, which was called Combination Index, showed synergism between the two agents in BCSCs as well as in the normal cells. Furthermore, BKM120 plus Herceptin showed more significantly suppression on following aspects in BCSCs and normal cancer cells : proliferation, invasion ability, colony forming as well as MFE. In addition, the levels of pAKT,pS6 in the BKM120 plus Herceptin group were decreased more obviously than those in control and monotherapy group respectively(p<0.05). Conclusions:BKM120 can inhibit the growth of normal cancer cells and BCSCs of SK-BR-3, by inhibiting cell proliferation, impairing the invasion abilities and the MFE, and reducing the expression of pAKT(Thr308,S473)and pS6(Thr389).Moreover, these results suggest that the combination of PI3K Inhibitor BKM120 with Herception may provide a novel therapy strategy for HER2+ BC. Citation Format: Jin Zhang, Feng Yu, Jingjing Liu, Xiaobei Zhang, Yunhui Hu. The effects of the BKM120 in combination with herceptin on HER2+ BC cells and BCSCs [abstract]. In: Proceedings of the Thirty-Seventh Annual CTRC-AACR San Antonio Breast Cancer Symposium: 2014 Dec 9-13; San Antonio, TX. Philadelphia (PA): AACR; Cancer Res 2015;75(9 Suppl):Abstract nr P6-12-08.