Root stem of Anemarrhena asPhodeloides was extracted with hot water,treated with ethanol and dilutealkali to temove protein. The polysaccharide thus obtained was given to mice by gastric gavage. Result showedthat the polysaccharide can marked1y lower the blood sugar and liver glycogen of mice without affecting bloodlipid level. When given intraperitoneally, it also showed hypoglycemic activity- For alloxan diabetic mice, thepolysaccharide can also markedly lower its b1ood sugar by gastric gavage.

Objective To assess the effect of suppression of insulin-like growth factor-1 receptor (IGF1R)in HO8910PM cell line by small interference RNA(siRNA).Methods Transfection of siRNA using liporectamine 2000 was conducted to silence IGF1R gene expression,the expression levels of IGF1R mRNA and protein were evaluated,and the effects on the cell cycles at 48 hours of transfection were assessed by real-time PCR,western blot and flow cytometry(FCM)assay respectively.The cell growth was detected by cell counting kit-8(CCK-8)at 24,48,72,96 hours of transfection.After 24 hours of transfection,the cells were cuhured with difierent concentrations of cisplatin(DDP)for 24 hours,the cell growth inhibition rate Was evaluated by CCK-8.Following incubation with 10μg/ml DDP for 24 hours after 24 hours of transfection,the apoptosis cells and the protein expression level of apoptosis-related gene,B cell leukemia/lymphoma 2(Bcl-2),were identified by FCM and western blot respectively.Resuits (1)Expression levels of IGF1R mRNA and protein were markedly decreased respectively at 48 hours of transfection IGF1R siRNA.(2)Suppression of IGF1R accompanied the reduction of cell growth at 48,72,96 hours of transfection with IGF1R siRNA,absorbance were 1.71±0.13,2.32±0.23,2.79±0.28 respectively (P＜0.01).(3)IGF1R siRNA induces arrest of G2 phase,the G2 phase rate of cells were 24.37%(P＜0.05).(4)Following treatment with 2.5,5,10,20μg/ml DDP for 24 hours after 24 hours of transfection,the cell growth inhibition rates were(25.94±0.08)%,(40.25±0.05)%,(59.48±0.03)%and(74.18±0.08)%respectively(P＜0.01).(5)Treatment with 10μg/ml DDP for 24 hours after 24 hours of transfection,induces 17.95%of cells apoptosis(P＜0.05),and decreases Bcl-2 protein level.Conclusion RNA interference of IGF1R gene induces the IGF1R silence in HO8910PM cell line significantly,inhibits cell growth in vitro, arrests the G2 phase, and enhances the chemosensitization to DDP.

ONYX-015 and H101 are E1B 55-kDa protein-deficient replicating C group adenoviruses that are currently in clinical trials as antitumor agents. However, their application in cancer gene therapy is limited by the native tropism of C group adenoviruses. This is in part due to low expression of the C group adenovirus receptor (coxsackievirus-adenovirus receptor, CAR) on malignant tumors. An H101-based chimeric virus vector containing sequences encoding the Ad35 fiber domain instead of the Ad5 fiber (H101-F35) was constructed. This modification allowed infection of tumor cells through CD46, a membrane protein over-expressed on tumors. The CAR and CD46 RNA expression was evaluated by RT-PCR method. H101-F35 conferred a stronger cytocidal effect than H101 and ONYX-015 in tumor cell lines that lacked CAR expression (MDA-MB-435 and MCF-7), while the cytocidal effect of H101-35, H101 and ONYX-015 was similar in high-level CAR expressing cancer cell lines (A549, NCI-H446, Hep3B, LNCaP, ZR-75-30 and Bcap-37). In an MDA-MB-435 xenograft mouse tumor model, tumor growth in mice receiving H101-F35 was significantly inhibited compared with mice injected with H101. These results suggest that the chimeric oncolytic adenovirus H101-F35 vector might be a useful candidate for gene therapy of cancer.

Uveal melanoma(UM)is the most frequent and life-threatening ocular malignancy in adults.Aberrant histone methylation contributes to the abnormal transcriptome during oncogenesis.However,a comprehensive understanding of histone methylation patterns and their therapeutic potential in UM remains enigmatic.Herein,using a systematic epi-drug screening and a high-throughput transcriptome profiling of histone methylation modifiers,we observed that disruptor of telomeric silencing-1-like(DOT1L),a methyltransferase of histone H3 lysine 79(H3K79),was activated in UM,especially in the high-risk group.Concordantly,a systematic epi-drug library screening revealed that DOT1 L inhibitors exhibited salient tumor-selective inhibitory effects on UM cells,both in vitro and in vivo.Combining Cleavage Under Targets and Tagmentation(CUT&Tag),RNA sequencing(RNA-seq),and bioinformatics analysis,we identified that DOT1 L facilitated H3K79 methylation of nicotinate phosphoribosyltransferase(NAPRT)and epigenetically activated its expression.Importantly,NAPRT served as an oncogenic accel-erator by enhancing nicotinamide adenine dinucleotide(NAD+)synthesis.Therapeutically,DOT1L inhi-bition epigenetically silenced NAPRT expression through the diminishment of dimethylation of H3K79(H3K79me2)in the NAPRT promoter,thereby inhibiting the malignant behaviors of UM.Conclusively,our findings delineated an integrated picture of the histone methylation landscape in UM and unveiled a novel DOT1L/NAPRT oncogenic mechanism that bridges transcriptional addiction and metabolic reprogramming.

The reversible and precise temporal and spatial regulation of histone lysine methyltransferases(KMTs)is essential for epigenome homeostasis.The dysregulation of KMTs is associated with tumor initiation,metastasis,chemoresistance,invasiveness,and the immune microenvironment.Therapeutically,their promising effects are being evaluated in diversified preclinical and clinical trials,demonstrating encouraging outcomes in multiple malignancies.In this review,we have updated recent understandings of KMTs'functions and the development of their targeted inhibitors.First,we provide an updated overview of the regulatory roles of several KMT activities in oncogenesis,tumor suppression,and im-mune regulation.In addition,we summarize the current targeting strategies in different cancer types and multiple ongoing clinical trials of combination therapies with KMT inhibitors.In summary,we endeavor to depict the regulation of KMT-mediated epigenetic landscape and provide potential epigenetic targets in the treatment of cancers.