Enhanced anti-tumor effects achieved in a murine tumor model using combination therapy of recombinant human manganese superoxide dismutase and adriamycin
Enhanced anti-tumor effects achieved in a murine tumor model using combination therapy of recombinant human manganese superoxide dismutase and adriamycin
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DOI：
10.1016/j.bbrc.2008.04.022
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发表时间：
2008-06-13
影响因子：
3.1
通讯作者：
Wu, Wu-Tong
中科院分区：
文献类型：
--
作者：
Chen, Che-Sheng;Zhao, Qing;Wu, Wu-Tong
锰超氧化物歧化酶（MnSOD）是线粒体中唯一的主要抗氧化酶，可清除超氧自由基。通过cDNA转染在癌细胞中过表达MnSOD抑制肿瘤形成并逆转恶性生长。在这项研究中，我们研究了重组人锰超氧化物歧化酶（rhMnSOD）单独和联合阿霉素（ADR）对癌症研究所（ICR）小鼠肉瘤180实体瘤的影响。rhMnSOD单用及与ADR联合应用均能显著抑制肿瘤生长，且呈剂量依赖性。rhMnSOD与ADR联合应用可增强ADR的抗肿瘤作用，而不增加ADR的毒性。组织学检查提供了抗肿瘤作用的证据。此外，我们发现肿瘤的淋巴细胞浸润，在治疗的肿瘤中CD4和CD8阳性细胞增加。随着rhMnSOD剂量的增加，CD4、CD8表达上调，联合ADR治疗进一步增强了这种上调作用。总的来说，这些数据表明，rhMnSOD可能通过刺激免疫系统和促进淋巴细胞募集到肿瘤中以杀死肿瘤细胞而表现出抗肿瘤作用。因此，MnSOD可能构成一个潜在的新的治疗剂，开发作为一种辅助治疗癌症。(c)2008年爱思唯尔公司All rights reserved.
Manganese superoxide dismutase (MnSOD) is the only primary antioxidant enzyme in mitochondria that scavenges superoxide radicals. Overexpressing MnSOD in cancer cells by cDNA transfection suppresses tumor formation and reverses malignant growth. In this study, we examined the effect of recombinant human manganese superoxide dismutase (rhMnSOD) alone and in combination with adriamycin (ADR) against solid tumors of sarcoma 180 in Institute of Cancer Research (ICR) mice. Administration of rhMnSOD alone and in combination with ADR significantly inhibited tumor growth in a dose-dependent manner. The use of rhMnSOD in combination with ADR enhanced ADR's anti-tumor potency without increasing toxicity. Histopathological examination provided evidence of the anti-tumor effect. In addition, we found lymphocyte infiltration of the tumors, with an increase in both CD4- and CD8-positive cells in the treated tumors. The expression of CD4 and CD8 was up-regulated with increasing dose of rhMnSOD, and the combination treatment with ADR further enhanced this up-regulation. Collectively, these data indicate that rhMnSOD may exhibit an anti-tumor effect by stimulating the immune system and promoting the recruitment of lymphocytes into the tumor to kill tumor cells. Thus MnSOD may constitute a potential new therapeutic agent to be exploited as an adjuvant in cancer therapy. (c) 2008 Elsevier Inc. All rights reserved.