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      저자 : Longhe Zhao (검색결과 2 건)
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        Realgar transforming solution suppresses angiogenesis and tumor growth by inhibiting VEGF receptor 2 signaling in vein endothelial cells

        Peng Song,Yang Hai,Xin Wang,Longhe Zhao,Baoqiang Chen,Peng Cui,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2018 Archives of Pharmacal Research Vol.41 No.4

        Realgar (As4S4), as an arsenic sulfide mineraldrug, has a good therapeutic reputation for anticancer inTraditional Chinese Medicine, and has recently beenreported to inhibit angiogenesis in tumor growth. However,considering the poor solubility and low bioavailability ofrealgar, large dose of realgar and long period of treatmentare necessary for achieving the effective blood medicineconcentration. In present study, we resolved the crucialproblem of poor solubility of realgar by using intrinsicbiotransformation in microorganism, and investigatedunderlying mechanisms of realgar transforming solution(RTS) for antiangiogenesis. Our results demonstrated thatRTS had a strong activity to inhibit HUVECs proliferation,migration, invasion, and tube formation. Moreover, RTSinhibited VEGF/bFGF-induced phosphorylation ofVEGFR2 and the downstream protein kinases includingERK, FAK, and Src. In vivo zebrafish and chickenchorioallantoic membrane model experiments showed thatRTS remarkably blocked angiogenesis. Finally, comparedwith the control, administration of 2.50 mg/kg RTSreached more than 50% inhibition against H22 tumorallografts in KM mice, but caused few toxic effects in thehost. The antiangiogenic effect was indicated by CD31immunohistochemical staining and alginate-encapsulatedtumor cell assay. In summary, our findings suggest thatRTS inhibits angiogenesis and may be a potential drugcandidate in anticancer therapy.

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        Realgar transforming solution-induced differentiation of NB4 cell by the degradation of PML/RARa partially through the ubiquitin–proteasome pathway

        Yang Hai,Xin Wang,Peng Song,Jian-yin Li,Longhe Zhao,Fei Xie,Xiang-min Tan,Qin-Jian Xie,Lan Yu,Yang Li,Zhengrong Wu,Hong Yu Li 대한약학회 2019 Archives of Pharmacal Research Vol.42 No.8

        PML/retinoic acid receptor alpha (RARa), as ahallmark of acute promyeloid leukemia (APL), is directlyrelated to the outcome of clinical APL remedy. It isreported that arsenicals can effectively degrade PML/RARa, such as arsenic trioxide and realgar. However, thehigh toxicity or insolubility have hampered their clinicalapplications. Realgar transforming solution (RTS) wasproduced from realgar by bioleaching process in our lab. Previous studies demonstrated that RTS had a significantanti-cancer ability on chronic myeloid leukemia throughoncoprotein degradation. The capacity of RTS on treatingAPL is what is focused on in this study. The results showedthat RTS had a noticeable sensitivity in NB4 cell, and RTSremarkably down-regulated PML/RARa expression andinduced cell differentiation. Further, RTS could accumulatePML/RARa into the nuclear bodies and then executedegradation, which could be reversed by proteasomeinhibitor MG132. The results also exhibited that thereduction of RTS-induced PML/RARa expression accompaniedby the elevation of ubiquitin and SUMO-1 proteinexpression. Finally, PML and SUMO-1 had been demonstratedto be co-localized after RTS treatment byimmunofluorescence co-localization assay and immunoprecipitationassay. In conclusion, these results suggestedthat RTS-induced cell differentiation may attribute to thePML/RARa degradation partially through the ubiquitin–proteasome pathway.

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