SB-T-121205, a next-generation taxane, enhances apoptosis and inhibits migration/invasion in MCF-7/PTX cells

摘要: Breast cancer is the leading cause of death among women. Paclitaxel, a mitotic inhibitor, highly effective in treatment breast cancer. However, development resistance to paclitaxel limits its clinical use. Identifying new compounds and strategies that are against cancer, particular drug-resistant great importance. aim present study was explore potential next-generation taxoid, SB-T-121205, modulating proliferation, migration invasion paclitaxel-resistant human cells (MCF-7/PTX) further evaluate underlying molecular mechanisms. The results MTT assay showed SB-T-121205 has much higher potency (MCF-7/S, MCF-7/PTX MDA-MB-453 cells) than paclitaxel, while non-tumorigenic bronchial epithelial (BEAS-2B) were slightly less sensitive paclitaxel. Flow cytometry western blot methods revealed induced cell cycle arrest at G2/M phase apoptosis through accelerating mitochondrial apoptotic pathway, resulting reduction Bcl-2/Bax ratio, as well elevation caspase-3, caspase-9, poly(ADP-ribose) polymerase (PARP) levels. Moreover, changed epithelial-mesenchymal transition (EMT) property, suppressed abilities cells. Additionally, exerted antitumor activity by inhibiting transgelin 2 PI3K/Akt pathway. These findings indicate potent agent promotes also recedes migration/invasion restraining PI3K/Akt, Such suggest value treatment.