【摘 要】
：
Liver is the most common metastatic site for colorectal cancer(CRC),there is no satisfied approach to treat CRC liver metastasis(CRCLM).Here,we investigated the role of a polycomb protein BMI-1 in CRCLM.Immunohistochemical analysis showed that BMI-1 expre
【机 构】
：
Biomedical Research Center,Sir Run Run Shaw Hospital,School of Medicine,Zhejiang University,Hangzhou
论文部分内容阅读
Liver is the most common metastatic site for colorectal cancer(CRC),there is no satisfied approach to treat CRC liver metastasis(CRCLM).Here,we investigated the role of a polycomb protein BMI-1 in CRCLM.Immunohistochemical analysis showed that BMI-1 expression in liver metastases was upregulated and associated with T4 stage,invasion depth and right-sided primary tumor.Knockdown BMI-1 in high metastatic HCT116 and LOVO cells repressed the migratory/invasive phenotype and reversed epithelial-mesenchymal transition(EMT),while BMI-1 overexpression in low metastatic Ls174T and DLD1 cells enhanced invasiveness and EMT.The effects of BMI-1 in CRC cells were related to upregulat-ing snail via AKT/GSK-3β pathway.Furthermore,knockdown BMI-1 in HCT116 and LOVO cells reduced CRCLM using experimental liver metastasis mice model.Meanwhile,BMI-1 overexpression in Ls174Tand DLD1 significantly increased CRCLM.Moreover,sodium butyrate,a histone deacetylase and BMI-1 inhib-itor,reduced HCT116 and LOVO liver metastasis in immunodeficient mice.Our results suggest that BMI-1 is a major regulator of CRCLM and provide a potent molecular target for CRCLM treatment.
其他文献
The intracellular retention of nanotherapeutics is essential for their therapeutic activity.The immobilization of nanotherapeutics inside target cell types can regulate various cell behaviors.However,strategies for the intracellular immobilization of nano
Nanocrystal formulations have been explored to deliver poorly water-soluble drug molecules.Despite various studies of nanocrystal formulation and delivery,much more understanding needs to be gained into absorption mechanisms and kinetics of drug nanocryst
Self-microemulsifying drug delivery systems(SMEDDSs)have recently returned to the lime-light of academia and industry due to their enormous potential in oral delivery of biomacromolecules.However,information on gastrointestinal lipolysis and trans-epithel
A major mitochondrial enzyme for protecting cells from acetaldehyde toxicity is aldehyde dehydrogenase 2 (ALDH2).The correlation between ALDH2 dysfunction and tumorigenesis/growth/metastasis has been widely reported.Either low or high ALDH2 expression con
The aim was to evaluate the potential of mucus-permeating nanoparticles for the oral admin-istration of insulin.These nanocarriers,based on the coating of zein nanoparticles with a polymer con-jugate containing PEG,displayed a size of 260 nm with a negati
In vitro-in vivo correlation(IVIVC)of solid dosage forms should be established basically between in vitro and in vivo dissolution of active pharmaceutical ingredients.Nevertheless,in vivo disso-lution profiles have never been accurately portrayed.The curr
Psoriasis is an autoimmune inflammatory disease,where dendritic cells(DCs)play an impor-tant role in its pathogenesis.In our previous work,we have demonstrated that topical delivery of curcumin-loaded poly(lactic-co-glycolic acid)(PLGA)nanoparticles(NPs)c
New approaches to cancer immunotherapy have been developed,showing the ability to harness the immune system to treat and eliminate cancer.For many solid tumors,therapy with checkpoint inhibitors has shown promise.For hematologic malignancies,adoptive and
The management of the central nervous system(CNS)disorders is challenging,due to the need of drugs to cross the blood-brain barrier(BBB)and reach the brain.Among the various strategies that have been studied to circumvent this challenge,the use of the int
This special APSB issue marks the beginning of a series of celebratory events for the 10-year anniversary of the journal.It was June 2011,when the first issue of the journal was published.It has been an exciting decade for the growth of the journal,which