The anti-tumor activator sMEK1 and paclitaxel additively decrease expression of HIF-1α and VEGF via mTORC1-S6K/4E-BP-dependent signaling pathways

摘要: // Boh-Ram Kim 1,* , Kyungsil Yoon Hyun-Jung Byun 1 Seung Hee Seo Seung-Hoon Lee 2 and Bae Rho Research Institute, National Cancer Center, 323, Ilsan-ro, Ilsandong-gu, Goyang-si Gyeonggi-do, Republic of Korea Department Life Science, Yong In University, 470, Samga-dong, Cheoin-gu, Yongin-si * These Authors contributed equally to this work Correspondence: Rho, email: Keywords : sMEK1 anti-activator; cell cycle arrest; caspase activity; traditional chemotherapeutic agent; ovarian cancer Received May 13, 2014 Accepted June 17, Published 19, Abstract Recently, we found that effectively regulates pro-apoptotic activity when combined with a drug. Therefore, combinational therapeutic strategies targeting critical molecular cellular mechanisms are urgently required. present work, evaluated whether enhanced the drugs in carcinoma cells. Combined drug, showed an additive effect on suppression growth by inducing arrest apoptosis regulating related gene expression levels or protein activities. addition, phosphoinositide-3-kinase (PI3K)/Akt/mammalian target rapamycin (mTOR) pathway was strongly inhibited treatment, showing de-repression tuberous sclerosis complex (TSC) ras homolog enriched brain (Rheb) mTOR raptor aggressive cells mouse xenograft models. Treatment paclitaxel reduced phosphorylation ribosomal S6 kinase (S6K) 4E-binding (4E-BP), two downstream targets mTOR-signaling pathway. Furthermore, both significantly signaling components S6K/4E-BP, such as hypoxia-inducible factor-1α (HIF-1α) vascular endothelial factor (VEGF), vitro vivo . our data suggest combination is promising effective targeted therapy for chemotherapy-resistant recurrent cancers.