p53蛋白是人体内十分重要的肿瘤抑制因子,通过调节细胞周期阻滞、诱导细胞凋亡等作用发挥肿瘤抑制功能。突变后的p53蛋白不仅具有显性负性效应(dominant negative effect,DN)抑制野生型p53蛋白功能,而且还通过功能获得性效应(gain of fu...p53蛋白是人体内十分重要的肿瘤抑制因子,通过调节细胞周期阻滞、诱导细胞凋亡等作用发挥肿瘤抑制功能。突变后的p53蛋白不仅具有显性负性效应(dominant negative effect,DN)抑制野生型p53蛋白功能,而且还通过功能获得性效应(gain of function,GOF)调节细胞代谢、侵袭、迁移等方式促进肿瘤的发生。p53蛋白在超过50%的肿瘤组织中发生突变,是肿瘤细胞区别于正常细胞的一个特异性药物靶点。因此,针对突变p53蛋白开发新型抗癌药物一直是研究的热点。长期以来,由于突变p53蛋白表面较为光滑,缺乏药物结合口袋,使其被认为是一个不可成药的靶点。随着高通量筛选技术的发展以及对突变p53蛋白结构的深入了解,许多靶向突变p53蛋白的小分子化合物被报道并在体外展现出较好的抗肿瘤活性,多款基于突变p53蛋白研发的化合物已经进入临床试验阶段。本文就靶向p53蛋白治疗肿瘤的直接和间接策略进行综述,重点针对突变p53蛋白重激活剂与降解突变p53蛋白的小分子化合物作用机制进行梳理,以期为后续开发靶向突变p53蛋白药物的创新提供帮助。展开更多
Doxorubicin is a commonly used chemotherapy drug for cancer treatment,although its effectiveness varies across different cancer types.p53 is a key factor involved in cell death induced by therapeutic agents,and it can...Doxorubicin is a commonly used chemotherapy drug for cancer treatment,although its effectiveness varies across different cancer types.p53 is a key factor involved in cell death induced by therapeutic agents,and it can be upregulated by doxorubicin,exhibiting a function of apoptosis.To further investigate the mechanism between p53 and doxorubicin,this study explored whether p53 plays a role in doxorubicin-induced cell death in the colorectal cancer line HCT116.The findings revealed that p53 was upregulated in HCT116 cells when treated with doxorubicin,and the knockdown of p53 decreased the sensitivity of HCT116 cells to doxorubicin.These results suggest that p53 plays an important role in doxorubicin-induced cell death in HCT116 cells,potentially contributing to more effective treatment approaches.展开更多
文摘p53蛋白是人体内十分重要的肿瘤抑制因子,通过调节细胞周期阻滞、诱导细胞凋亡等作用发挥肿瘤抑制功能。突变后的p53蛋白不仅具有显性负性效应(dominant negative effect,DN)抑制野生型p53蛋白功能,而且还通过功能获得性效应(gain of function,GOF)调节细胞代谢、侵袭、迁移等方式促进肿瘤的发生。p53蛋白在超过50%的肿瘤组织中发生突变,是肿瘤细胞区别于正常细胞的一个特异性药物靶点。因此,针对突变p53蛋白开发新型抗癌药物一直是研究的热点。长期以来,由于突变p53蛋白表面较为光滑,缺乏药物结合口袋,使其被认为是一个不可成药的靶点。随着高通量筛选技术的发展以及对突变p53蛋白结构的深入了解,许多靶向突变p53蛋白的小分子化合物被报道并在体外展现出较好的抗肿瘤活性,多款基于突变p53蛋白研发的化合物已经进入临床试验阶段。本文就靶向p53蛋白治疗肿瘤的直接和间接策略进行综述,重点针对突变p53蛋白重激活剂与降解突变p53蛋白的小分子化合物作用机制进行梳理,以期为后续开发靶向突变p53蛋白药物的创新提供帮助。
文摘Doxorubicin is a commonly used chemotherapy drug for cancer treatment,although its effectiveness varies across different cancer types.p53 is a key factor involved in cell death induced by therapeutic agents,and it can be upregulated by doxorubicin,exhibiting a function of apoptosis.To further investigate the mechanism between p53 and doxorubicin,this study explored whether p53 plays a role in doxorubicin-induced cell death in the colorectal cancer line HCT116.The findings revealed that p53 was upregulated in HCT116 cells when treated with doxorubicin,and the knockdown of p53 decreased the sensitivity of HCT116 cells to doxorubicin.These results suggest that p53 plays an important role in doxorubicin-induced cell death in HCT116 cells,potentially contributing to more effective treatment approaches.
