The promotion of human malignant melanoma growth by mesoporous silica nanoparticles through decreased reactive oxygen species.
The concept that mesoporous silica nanoparticles (MSNs) are regarded as ideal novel drug delivery carriers in tumor therapy has been introduced extensively, but the effects of MSNs on tumor growth have received little attention. Here a model of nude mice xenografted with human malignant melanoma cells (A375) was used to investigate the effect of MSNs on tumor growth. Surprisingly, we found that MSNs have no toxicity to human malignant melanoma but increasing tumor growth in vivo. It was also confirmed that MSNs significantly promoted A375 cell proliferation and accelerated cell cycle progression in vitro. Cellular uptake mechanism showed that MSNs may affect molecular behavior of A375 cells when they entered into cytoplasm. Then, a detailed mechanism indicated that the promotion effect induced by MSNs was due to the decreasing of endogenous reactive oxygen species (ROS) in cells. Further results demonstrated that the upregulation of anti-apoptotic molecules Bcl-2 expression and the inhibition of NF-kappaB activation by MSNs may promote cell proliferation in a redox-sensitive signal pathway. These results show that tumor growth can be regulated by nanocarriers themselves in a ROS-dependent manner and imply that nanocarriers are not necessarily suitable for all kinds of tumor therapy in development drug delivery system.
Laboratory of Controllable Preparation and Application of Nanomaterials, Technical Institute of Physics and Chemistry, Chinese Academy of Sciences, Beijing 100190, China.
Xinglu
X
Huang
Jie
J
Zhuang
Xu
X
Teng
Linlin
L
Li
Dong
D
Chen
Xiyun
X
Yan
Fangqiong
F
Tang
D000818:Animals; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D000075202:Contraindications; D004705:Endocytosis / Q000187:drug effects; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D042541:Intracellular Space / Q000187:drug effects / Q000378:metabolism; D008545:Melanoma / Q000378:metabolism* / Q000473:pathology*; D051379:Mice; D016328:NF-kappa B / Q000378:metabolism; D053758:Nanoparticles / Q000009:adverse effects* / Q000648:ultrastructure; D010084:Oxidation-Reduction / Q000187:drug effects; D016062:Porosity / Q000187:drug effects; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D017382:Reactive Oxygen Species / Q000378:metabolism*; D015398:Signal Transduction / Q000187:drug effects; D012822:Silicon Dioxide / Q000009:adverse effects*; D023041:Xenograft Model Antitumor Assays
D016328:NF-kappa B; D019253:Proto-Oncogene Proteins c-bcl-2; D017382:Reactive Oxygen Species; D012822:Silicon Dioxide; D005978:Glutathione