Treatment of triple negative breast cancer cells with combination of mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901

VernacularTitle:联合mTOR1/2抑制剂AZD8055和MEK1/2抑制剂PD0325901抑制三阴乳腺癌细胞研究
Author: Xi-yan NAN ¹ ; Yun WU ¹ ; Li-he ZHANG ¹ ; Zhen-jun YANG ¹
Author Information

1. State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing 100191, China
Publication Type:ORIGINAL ARTICLES
Keywords: triple negative breast cancer; mTOR1/2 inhibitor; MEK1/2 inhibitor; dual combination
From: Acta Pharmaceutica Sinica 2016;51(10):1551-
CountryChina
Language:Chinese
Abstract: MEK inhibition activates PI3K/AKT/mTOR pathway in triple negative breast cancer (TNBC) cell lines. Combination of PI3K inhibitor and MEK1/2 inhibitor is not appropriate for PI3K inhibitor insensitive TNBC cell lines. This study was designed to investigate the effects of dual treatments with mTOR1/2 inhibitor AZD8055 and MEK1/2 inhibitor PD0325901 in MDA-MB-435 cell line. MEK1/2 inhibition led to activation of AKT, which is the downstream signaling protein of PI3K pathway. The combination inhibited the phosphorylation of AKT and therefore abolished the feedback interaction of two pathways. Cell proliferation assay and DNA replication assay demonstrated that the dual treatments led to a significant synergistic inhibition of cell cycle progression and cell proliferation.