Withaferin A arrested glioblastoma cells at G2/M phase and induced apoptosis through intrinsic pathway

OBJECTIVE To explore the efficacy and mechanism of withaferin A(WA)in Glioblastoma multiforme(GBM,WHO gradeⅣastrocytoma).METHODS Cell viability assay and nude mice xenograft model were used to evaluate the efficacy of WA in GBM.Flow cytometry was performed to detection the effects of WA on apoptosis and cell cycle of GBM.Western blotting and siRNA transfection were carried out to check signaling pathway induced by WA.RESULTS WA significantly inhibited the growth of GBM in vivo and in vitro.WA treatment triggered the intrinsic apoptosis of GBM cells by upregulating expression of Bim and Bad,and arrested GBM cells at G2/M phase through dephosphorylating Thr161 of CDK1 by activating p53-independent p21 up-regulation.In addition,p21 knockdown restored progress of cell cycle and cell viability by down-regulating the expression of Bad rather than Bim.CONCLUSION WA arrested GBM cells at G2/M phase and triggered the intrinsic apoptosis through p21-Bad axis.

抗衰老靶点及药物的研究进展

衰老是指随着年龄的增长,机体生理功能发生不可逆转的逐渐衰退的过程。随着人们对衰老相关机制研究的不断深入,寻找有效的抗衰老药物并通过药物干预的手段延缓衰老、延长寿命已成为当前抗衰老研究领域中的热点问题。近年来一系列不同来源的化合物被发现具有潜在的抗衰老活性,其中一些已经进入临床试验阶段,推动抗衰老药物的研究的不断发展。笔者介绍衰老的概念以及衰老相关的信号通路和靶点,并总结了近年来抗衰老药物相关研究的最新进展,对衰老及抗衰老药物研究的未来发展趋势进行展望。

肿瘤免疫和代谢药物靶点研究进展

肿瘤的发生发展与肿瘤微环境密切相关。其中,肿瘤免疫微环境和肿瘤代谢微环境对肿瘤的发生发展和侵袭转移起着重要作用。肿瘤免疫治疗是通过激活人体本身的免疫系统或使免疫正常化从而起到杀伤或抑制肿瘤生长的作用。肿瘤免疫疗法已在多种实体瘤中表现出良好的治疗效果。近年来,针对肿瘤的免疫治疗取得了一些显著的进展。Warburg效应表明肿瘤细胞主要通过有氧糖酵解获取能量,肿瘤中能量代谢发生异常,肿瘤微环境会诱发肿瘤细胞代谢发生重编程。因此,靶向肿瘤代谢对肿瘤治疗也具有十分重要的意义。本文对近年来肿瘤免疫和肿瘤代谢的主要药物靶点及其相关药物研发进展进行了综述。

胰腺癌药物靶点及治疗药物的研究进展

胰腺癌是一种恶性程度高、患者总体预后不良的肿瘤。高异质性、复杂的肿瘤微环境、耐药性更是加剧了胰腺癌治疗的困难性。目前,吉西他滨联合卡培他滨、白蛋白紫杉醇等以及FOLFIRINOX是可切除或晚期转移性胰腺癌的标准化学疗法。鉴于化疗疗效有限且伴随毒副作用,近来靶向药物及免疫治疗药物逐渐引起重视并取得一定进展。本文将对胰腺癌的化疗药物、靶点及靶向药物、免疫治疗药物进行系统综述。