癌细胞
化学
血管生成
癌症研究
CD44细胞
癌症
基因沉默
小干扰RNA
细胞生物学
细胞
生物
生物化学
医学
内科学
转染
基因
作者
Vahid Karpisheh,Javad Fakkari Afjadi,Mohsen Nabi‐Afjadi,Melika Sadat Haeri,Tayebeh Sadat Abdpoor Sough,Sim Heydarzadeh Asl,Mehdi Edalati,Fatemeh Atyabi,Ali Masjedi,Farnaz Hajizadeh,Sepideh Izadi,Farnaz Sadat Mirzazadeh Tekie,Maliheh Hajiramezanali,Mozhdeh Sojoodi,Farhad Jadidi‐Niaragh
标识
DOI:10.1016/j.ijbiomac.2020.11.056
摘要
Increased expression of Hypoxia-inducible factor-1α (HIF-1α) in the tumor microenvironment, mainly due to tumor growth, plays a major role in the growth of cancer. Tumor cells induce the expression of cyclooxygenase 2 (COX2) and its product, prostaglandin E2 (PGE2), through overexpression of HIF-1α. It has been shown that ligation of PGE2 with its receptor, EP4, robustly promotes cancer progression. HIF-1α/COX2/PGE2/EP4 signaling pathways appear to play an important role in tumor growth. Therefore, we decided to block the expansion of cancer cells by blocking the initiator (HIF-1α) and end (EP4) of this pathway. In this study, we used hyaluronate (HA), and trimethyl chitosan (TMC) recoated superparamagnetic iron oxide nanoparticles (SPIONs) loaded with HIF-1α-silencing siRNA and the EP4 antagonist (E7046) to treat cancer cells and assessed the effect of combination therapy on cancer progression. The results showed that optimum physicochemical characteristics of NPs (size 126.9 nm, zeta potential 27 mV, PDI < 0.2) and linkage of HA with CD44 molecules overexpressed on cancer cells could deliver siRNAs to cancer cells and significantly suppress the HIF-1α in them. Combination therapy of cancer cells by using HIF-1α siRNA-loaded SPION-TMC-HA NPs and E7046 also prevent proliferation, migration, invasion, angiogenesis, and colony formation of the cancer cells, remarkably.
科研通智能强力驱动
Strongly Powered by AbleSci AI