An anti-double-stranded DNA monoclonal antibody induced by tumor cell-derived DNA inhibits the growth of tumor in vitro and in vivo via triggering apoptosis
An anti-double-stranded DNA monoclonal antibody induced by tumor cell-derived DNA inhibits the growth of tumor in vitro and in vivo via triggering apoptosis
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由肿瘤细胞来源的DNA诱导的抗双链DNA单克隆抗体通过触发细胞凋亡抑制体外和体内肿瘤的生长
DOI：
10.1089/dna.2007.0633
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发表时间：
2008-02-01
影响因子：
3.1
通讯作者：
Xiong, Sidong
中科院分区：
文献类型：
--
作者：
Cao, Qinghua;Xu, Wei;Xiong, Sidong
抗双链DNA（抗dsDNA）抗体的血清学存在是癌症患者中的常见现象。一些抗dsDNA抗体水平相对较高的患者可能具有较好的预后，表明抗dsDNA抗体的潜在抗肿瘤作用。为了阐明抗dsDNA抗体在延缓肿瘤发展中的作用和机制，我们制备了一组抗dsDNA单克隆抗体（mAb），并评估了它们在体外和体内的抗肿瘤作用。用SP2/0肿瘤细胞DNA免疫BALB/c小鼠，获得12株抗dsDNA单克隆抗体。其中，mAb 2G 8在体外对Wehi 164细胞的杀伤作用最强，在体内对肿瘤生长有明显的抑制作用。这种mAb 2G 8 - 1介导的抗肿瘤作用主要通过触发细胞凋亡来发挥，如Annexin V染色和DNA片段化所证明的。抗凋亡基因Bcl-2和Bcl-xL的表达下调，促凋亡基因Bax的表达上调，提示线粒体凋亡途径参与了凋亡过程。因此，抗dsDNA单抗2G 8具有诱导细胞凋亡的抑瘤活性，为肿瘤干预方法的研究提供了新的思路。
Serological presence of anti-double-stranded DNA (anti-dsDNA) antibodies is a common phenomenon in cancer patients. Some patients with relatively high levels of anti-dsDNA antibodies may have a better prognosis, indicating the potential antitumor roles of anti-dsDNA antibodies. To delineate the role and mechanisms of anti-dsDNA antibodies in delaying tumor development, here we prepared a panel of anti-dsDNA monoclonal antibodies (mAbs) and assessed their antitumor effects both in vitro and in vivo. After immunization of BALB/c mice with DNA from SP2/0 tumor cells, 12 anti-dsDNA mAbs were obtained. Among these mAbs, mAb 2G8 exhibited the strongest cytotoxicity to Wehi164 cells in vitro and significantly inhibited the growth of tumor in vivo. This mAb 2G8-.mediated antitumor effect was mainly exerted by triggering apoptosis, as evidenced by Annexin V staining and DNA fragmentation. Further, the expression of antiapoptotic genes Bcl-2 and Bcl-xL was downregulated while that of pro-apoptotic gene Bax was upregulated, suggesting the involvement of mitochondrial apoptotic pathway. Taken together, dsDNA-specific mAb 2G8 revealed promising tumor-suppressive activity by inducing apoptosis, which provides a possible new strategy for the development of tumor intervening methods.