Enhanced anti-tumor effects achieved in a murine tumor model using combination therapy of recombinant human manganese superoxide dismutase and adriamycin.
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.
Chen
Che-Sheng
CS
School of Life Science and Technology, China Pharmaceutical University, No. 24 Tongjiaxiang, Nanjing, Jiangsu Province 210009, China.
Zhao
Qing
Q
Wang
Jia
J
Rong
Jing-Jing
JJ
Yuan
Qin-Sheng
QS
Guo
Qing-Long
QL
Wu
Wu-Tong
WT
D000818:Animals; D000971:Antineoplastic Combined Chemotherapy Protocols; D015496:CD4-Positive T-Lymphocytes / Q000276:immunology; D018414:CD8-Positive T-Lymphocytes / Q000276:immunology; D004195:Disease Models, Animal; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D016246:Lymphocytes, Tumor-Infiltrating; D051379:Mice; D011994:Recombinant Proteins / Q000627:therapeutic use*; D012510:Sarcoma 180 / Q000188:drug therapy* / Q000276:immunology / Q000473:pathology; D013482:Superoxide Dismutase / Q000627:therapeutic use*
D011994:Recombinant Proteins; D004317:Doxorubicin; D013482:Superoxide Dismutase