促凋亡基因Bax在胰腺癌中的研究进展

The research advancement of proapoptosis gene Bax on pancreatic cancer

胰腺癌的恶性程度高、转移早、浸润性强,这与胰腺癌的细胞凋亡异常有密切的关系。Bax是目前研究最深入的促凋亡基因之一。多数研究认为,Bax在胰腺癌中存在高表达,其表达率从53%到100%不等。有研究认为Bax的表达预示着胰腺癌的良性预后,也有研究发现胰腺癌中Bax的表达与胰腺癌的分级分化等有关。Bax在胰腺癌中的表达受p53、PERIOD1、P13K/AKT等的调控。Bax表达异常及其突变可能与胰腺癌的发生有关。研究发现Bax表达可增强胰腺癌对吉西他滨和5-FU等化疗药物以及放射治疗的敏感性,而Bax/Bcl-2的比值可能与胰腺癌放化疗敏感性更相关。提高Bax基因表达、上调Bax活性等针对Bax的靶向治疗已显示出促进胰腺癌细胞凋亡、增强药物抗癌效应的作用。同时,作为最重要的促凋亡蛋白之一,Bax成为评价各种抗胰腺癌药物的疗效、探讨其作用机制的重要指标之一。对胰腺癌中Bax的深入研究,有利于了解其与胰腺癌的预后和耐药性的关系,为胰腺癌的靶向治疗提供新的方向。

Pancreatic cancer is a high malignancy with early metastasis and invasion,which has a correlation with abnormability of cell apoptosis.Bax is a proapoptotic factor studied most in-depth.In most researches,Bax was found a high expression from 53%to 100%in pancreatic cancer.Some studies showed Bax expression was significantly associated with a better prognosis,and Bax contributed to the classification and differentiation of pancreatic cancer.P53,PERIOD1 and P13K/AKT was responsible in the regulation of Bax.Expression of Bax may sensitize human pancreatic cancers to apoptosis induced by chemotherapeutic agents such as gemcitabine, 5-FU,and enhance radiosensitivities,while the Bcl-2/Bax ratio may contribute more than single Bax.Targeted therapy such as overexpression of Bax gene,enhancing the activity of Bax protein demonstrated to promote the cancer cell apoptosis and enhance the effect of common chemotherapeutics.As the most important proapoptotic protein,Bax becomes an important index in evaluation and investigation of antitumor effects or pharmacomechanism.The penetrating research of Bax in pancreatic cancer contributes to acknowledge the relationship between Bax and prognosis or drug resistance,which may lead to a new trend in targeted therapy.