前沿医讯

前沿医讯

　　粤科研团队发现一系列药物可逆转多药抗药性

粤科研团队发现一系列药物可逆转Multi-drug resistance

　　本报讯 (记者任珊珊 通讯员黄金娟、欧晓芳)肿瘤细胞产生抗药性，是导致化疗失败、病人死亡的最主要原因。记者从中山大学肿瘤防治中心获悉，由中山大学肿瘤防治中心实验研究部主任符立梧教授领衔的科研团队，发现一系列药物可逆转或抑制肿瘤的多药抗药性。这一基础研究成果为肿瘤病人带来新希望。目前，该系列研究成果已经在多份国际权威学术期刊发表，其中包括Cancer Res (《癌症研究》)、Mol Med(《分子医学》)等SCI论文73篇，获得专利6项。去年，该研究获广东省科技进步奖一等奖和中国抗癌协会科技奖。

本报讯 (Reporter ren shan correspondent Huang Jinjuan/Ou XiaoFang)Resistant tumor cells,Is lead to chemotherapy failure/病people死亡的最主要原因.The reporter learns from sun yat-sen university cancer prevention and control center,By sun yat-sen university cancer prevention and control center for experimental research at scientific research team, led by professor FuLiWu director,Find a series of drugs can reverse or inhibit tumor multi-drug resistance.这一基础研究成果为肿瘤病people带来新希望.At present,该系列研究成果已经In the多份国际权威学术期刊发表,Including Cancer Res ([For research on cancer])/Mol Med([Molecular medicine])Such as SCI, 73 papers,Patented 6 items.Last year,,The study was awarded the first prize for science and technology progress prize in guangdong province and China anti-cancer association awards.

　　两大因素导致化疗失败 两大因素导致化疗失败

　　全身化疗是治疗肿瘤的主要手段，可以减少或者消除肿瘤的复发及转移。然而，目前有两大主要因素制约了化疗的成功率：一是抗肿瘤药物具有毒性，二是肿瘤细胞对抗癌药物的抗药性，尤其是“多药抗药性”，是癌症死亡病人的最主要死因，约占死亡病人的九成。

全身化疗是治疗肿瘤的主要手段,Can reduce or eliminate the tumor recurrence and metastasis.however,At present有两大主要因素制约了化疗的成功率:A toxic is antitumor drugs,Second, the tumor cells to anticancer drug resistance,Especially in the"Multi-drug resistance",是癌症死亡病people的最主要死因,约占死亡病people的九成.

　　“肿瘤细胞对一种抗癌药物产生抗药性时，对结构及作用机制不同的其他抗癌药物也会产生交叉抗药性。”符立梧介绍，这种“多药抗药性”是肿瘤化疗失败的最重要原因，目前临床上仍无良策。

"When tumor cells resistant to an anticancer drug,The structure and mechanism of different anti-cancer drugs also can produce other cross resistance."FuLiWu introduction,This kind of"Multi-drug resistance"Is the most important reason to tumor chemotherapy failure,At present临床上仍无良策.

　　“肿瘤耐药的最重要原因，是肿瘤细胞膜上的‘ABC转运泵’在肿瘤干细胞中的过度表达。”符立梧表示，“ABC转运泵”的家族有49个成员，其中11个与多药抗药性有关。其中，最重要的当属ABCB1/P-gp、ABCC1/MRP1、ABCG2/BCRP这三种跨膜蛋白的过度表达。它们可将抗癌药物泵出细胞外，使抗癌药物在肿瘤细胞中的浓度降低，从而令肿瘤细胞产生抗药性。

"The most important reason for tumor drug resistance,Is on the tumor cell membrane‘The ABC transport pump’In the肿瘤干细胞中的过度表达."FuLiWu said,"The ABC transport pump"The family has 49 members,11 of them are associated with multi-drug resistance.Among them,The most important is the ABCB1 / P - gp/ABCC1 / MRP1/ABCG2 / BCRP across the three membrane protein overexpression.They can be to pump anti-cancer drugs out of cells,使抗癌药物In the肿瘤细胞中的浓度降低,Resistant to tumor cells.

　“老药新用”可抗癌 "Old drugs with new"Can be cancer

　　从1993年开始，符立梧教授领衔的团队致力于解决肿瘤多药抗药性问题，迄今已发表142篇具有重要影响的论文。该团队在世界上首次报道多种酪氨酸激酶抑制剂(TKIs)能对ABC转运泵导致的抗药性进行逆转，能增强传统抗癌药物对肿瘤干细胞的杀灭作用。这为临床上TKIs与传统抗癌药物的联合应用提供依据。

从1993年开始,FuLiWu professor leading the team to solve the problem of tumor multi-drug resistance,Have so far published 142 paper has the important influence.该团队In the世界上首次报道多种酪氨酸激酶抑制剂(TKIs)Resistance can be induced to ABC transport pump in reverse,Can enhance traditional anti-cancer drugs to cancer stem cell killing effect.For the clinical TKIs and provides the reference for the combined application of traditional anti-cancer drugs.

　　该团队与美国圣约翰大学合作，经小鼠实验显示，传统用于治疗男性阳痿的明星药物西地那非(“伟哥”)以及粉防己碱等，在体内外均可以逆转抗药性，且对抗癌药物的药效没有影响，实现“老药新用”。四川学者在这一成果的基础上，研发出溴化粉防己碱药物，已进入临床试验阶段。该团队还自主研发出第三代多药抗药性逆转剂FG020326(咪唑类衍合物)。此外，该团队将原本用于植物研究领域的siRNA技术，首次用于肿瘤研究领域，发现将编码跨膜蛋白ABCB1的mdr1基因“沉默”后，可让出现抗药性的肿瘤细胞提高对抗癌药物的敏感性。

该团队与美国圣约翰大学合作,Through the experiment in mice suggests,Traditional star drugs used in treatment of male impotence sildenafil("viagra")And powder has alkali proof, etc,In the体内外均可以逆转抗药性,And has no effect on the efficacy of anti-cancer drugs,To achieve"Old drugs with new".四川学者In the这一成果的基础上,Developed bromide powder anti alkaline drugs,Has entered the stage of clinical trials.The team also independently developed the third generation of multidrug resistance reversal agents FG020326(Imidazoles yan compound).In addition,The team will originally used in the study of plants in the field of siRNA technology,Used for the field of cancer research for the first time,Discovery will code across a membrane protein ABCB1 mdr1 gene"silence"after,Can increase of the drug resistance of tumor cells to anticancer drug sensitivity.

　　近年来，符立梧团队还发现从天然植物中提取、合成的化合物如姜黄素衍生物、泡番荔枝辛、黑麦酮酸D，对多药抗药性肿瘤细胞也具有抗癌作用。这一研究为开发新型抗癌药物奠定基础。

近年来,FuLiWu team also found that extracted from natural plants/Synthesis of compounds such as curcumin derivatives/Bubble cherimoya sheen/Rye keto acid D,For multi-drug resistant tumor cells also have anti-cancer effect.This study lay a foundation for the development of new anti-cancer drugs.

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　　本报4月28日见报的《丙肝治疗或将“抛弃”干扰素》内文提到“干扰素副作用大，且服用不方便，而且还有20%左右的病人用聚乙二醇干扰素α联合利巴韦林抗病毒治疗效果不好”，为免患者误解，补充说明如下：目前干扰素加利巴韦林还是中国丙肝治疗的金标准，在此基础上联合使用小分子药物蛋白酶抑制剂效果更佳。

本报4月28日见报的[Hepatitis c treatment or will"abandon"interferon]Nevin mentioned"Side effects of interferon,And use not convenient,而且还有20%左右的病people用聚乙二醇interferonα联合利巴韦林抗病毒治疗效果不好",Patients in order to avoid misunderstanding,Add the following:At presentinterferon加利巴韦林还是中国丙肝治疗的金标准,In the此基础上联合使用小分子药物蛋白酶抑制剂效果更佳.