(精选)【医学课件】Emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2neu in Her2neu-overexpressing cancer cells教学课件.pptVIP

中山大学肿瘤防治中心 SUN YAT-SEN UNIVERSITY CANCER CENTER Emodin azide methyl anthraquinone derivative induces proteasomal degradation of Her2/neu in Her2/neu-overexpressing cancer cells Li-sheng Zheng, Yan-yan Yan, Li-wu Fu Cancer Center, Sun Yat-sen University 2010. 5 ? Overexpression of HER2/neu is common in multiple malignancies, including breast, ovarian, lung and prostate cancer, etc. ? Clinical studies have demonstrated that elevated HER2/neu expression correlates with poor prognosis in multiple malignancies ? During the last decade, HER2/neu has been targeted in order to develop novel anticancer drugs Trastuzumab (Herceptin?) Lapatinib (Tykerb) ------ efficacy and long-term use in patients are quite limited due to resistance to these inhibitors or severe side effects Background ? Anthraquinone derivative ? Active ingredient of various Chinese herbs including rhubarb, Polygonum cuspidatum ? Anti-bacterial, anti-inflammatory, anti-tumor Emodin Structure of emodin Background ? Block auto- or trans-phosphorylation of HER2/neu ? Increases the susceptibility of HER2/neu overexpressing cancer cells to standard cytotoxic therapeutic agents ? anticancer activity not obvious ? side effects such as cardiac toxicity ? We and Professor Lian-quan Gu group (School of Chemistry and Chemical Engineering, Sun Yat-sen University) modified structure of emodin and synthesized a series of emodin anthraquinone derivatives Background Structure of emodin AMAD AMAD shows potent anticancer effect on breast cancer and lung adenocarcinoma cell lines AMAD inhibits the growth of human non-small cell lung carcinoma H460 cell xenografts in nude mice AMAD down-regulates Her2/neu protein expression AMAD inhibits Her2/neu downstream signaling pathways AMAD inhibited Her2/neu binding to Hsp90 Knockdown Her2/neu by siRNA induces growth inhibition * * 中山大学肿瘤防治中心 SUN YAT-SEN UNIVERSITY CANCER CENTER