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胰腺癌是一种预后极差的恶性消化道肿瘤,5年生存率小于5%,这与胰腺癌细胞的凋亡异常有着密切的关系。Bad基因是Bcl-2家族中的一种促凋亡基因,被认为可以通过浓度依赖性方式替换Bcl-xL/Bax、Bcl-2/Bax二聚体中的Bax,从而达到促进细胞凋亡、防止胰腺癌的发生。Bad基因在胰腺癌中的调控主要以磷酸化/去磷酸化调控最为常见,研究显示,胰腺癌中Bad表达总量变化不明显,而在Ser112位点上的磷酸化为灭活的pBad112形式表达却明显增多。胰腺癌中过表达的14-3-3sigma、Pim-3、cAMP等均可诱导Bad蛋白磷酸化,而PKC、MAP4K3等可诱导其去磷酸化。同时,针对Bad的靶向治疗在胰腺癌中的应用研究已经有所进展,其中有研究发现人参皂苷Rg3、Cantharidin、Stemonamid等药物均可通过Bad途径促胰腺癌细胞凋亡。对胰腺癌中的Bad的深入研究,有利于了解其与胰腺癌发病机制的关系,为胰腺癌的靶向治疗提供新的方向。
Pancreatic cancer is a malignant gastrointestinal cancer with poor prognosis. The 5-year survival rate is less than 5%, which is closely related to the abnormal apoptosis of pancreatic cancer cells. Bad gene, a pro-apoptotic gene in Bcl-2 family, is thought to be able to replace Bax in Bcl-xL / Bax and Bcl-2 / Bax dimers in a concentration-dependent manner to promote cell apoptosis, Prevent the occurrence of pancreatic cancer. The regulation of Bad gene in pancreatic cancer is mainly controlled by phosphorylation / dephosphorylation. The study shows that there is no obvious change in the total amount of Bad expression in pancreatic cancer, while the phosphorylation at Ser112 site is inactivated expression of pBad112 But significantly increased. Pancreatic cancer overexpression of 14-3-3sigma, Pim-3, cAMP, etc. can induce Bad protein phosphorylation, and PKC, MAP4K3 can induce its dephosphorylation. At the same time, the targeted therapy of Bad has been applied in pancreatic cancer. Some studies have found that Ginsenoside Rg3, Cantharidin, Stemonamid and other drugs can promote the apoptosis of pancreatic cancer cells through the Bad pathway. The in-depth study of Bad in pancreatic cancer is helpful to understand its relationship with the pathogenesis of pancreatic cancer and provide a new direction for the targeted therapy of pancreatic cancer.