错配修复系统缺陷对肿瘤放化疗的影响

在肿瘤干细胞和增殖性肿瘤细胞中,广泛存在错配修复(MMR)系统的功能缺失。对于接受化疗的肿瘤,若MMR缺失,可导致细胞绕过细胞周期的G2/S期循环阻滞,产生对化疗药物的抗性。在I临床上,即使是06-甲基鸟嘌呤-DNA甲基转移酶阴性的胶质瘤细胞也会因MMR的缺失,对替莫唑胺产生抗性。对于接受放射治疗的肿瘤,MMR缺失的作用表现为相互矛盾的两个方面:首先,MMR缺失可导致肿瘤细胞对辐射挠陛的提高,细胞不出现凋亡和自吞噬;另一方面,预先给予放射增敏剂5-碘-2'-脱氧尿苷(IUdR)等药物后,MMR的缺失会导致DNA中掺杂大量未被修复的IUdR等基团,从而提高肿瘤细胞的辐射敏感性。

The effect of mismatch repair deficiency on chemotherapy and radiotherapy in tumors

It is very common phenomenon that mismatch repair (MMR) deficiency in various tumors, both stem cells and proliferation cells.With MMR deficiency,the cells treated by chemotherapy drugs passed the G₂/S arrest and became resistant to the drugs.In the clinical trial,even in the glioma with negative 06-methylguanine-DNA methyhransferase expression show the resistance to Temozolomide.The MMR deficiency cells treated by radiotherapy show two contradictory behaviors.MMR deficiency enhanced the cells resistance to radiation,for cells show less apoptosis or autophagy.On the other hand,pretreated with radiation enhancer,such as 5-iodo-2'-deoxyuridine (IUdR),resulting in more IUdR-DNA unrepaired cells and increasing the sensitivity to radiation.