Intratumoral injection of pEGFC1-IGFBP7 inhibits malignant melanoma growth in C57BL/6J mice by inducing apoptosis and down-regulating VEGF expression.
Malignant melanoma (MM) is a type of aggressive skin cancer, and the effective therapy for MM is highly desired. Recently, genome-wide RNA interference screening study revealed that loss of expression of insulin-like growth factor binding protein 7 (IGFBP-7) is a critical step in development of MM, and this secreted protein plays a central role in apoptosis of MM. Furthermore, a prostatic carcinoma cell line stably transfected with IGFBP-7 cDNA showed poor tumorigenicity. Thus, we supposed it to be an efficacious agent for inhibiting melanomas. In this study, we constructed pEGFC1-IGFBP7 to try to obtain high expression of IGFPB7 and then we demonstrated that this plasmid inhibited proliferation of B16-F10 melanoma cells efficiently in vitro. Moreover, intratumoral injection of pEGFC1-IGFBP7 inhibited MM growth in C57BL/6J mice. The inhibition of MM growth is due to apoptosis and reduced expression of VEGF induced by pEGFC1-IGFBP7. These results suggest a potential new clinical strategy for MM treatment.
Chen
Rong-Yi
RY
Department of Dermatology, Affiliated Union Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430022, PR China. xhcry@yahoo.cn
Chen
Hong-Xiang
HX
Jian
Ping
P
Xu
Li
L
Li
Juan
J
Fan
Yi-Ming
YM
Tu
Ya-Ting
YT
D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015153:Blotting, Western; D019496:Cancer Vaccines / Q000235:genetics / Q000378:metabolism / Q000627:therapeutic use*; D053148:Caspase 3 / Q000096:biosynthesis / Q000187:drug effects; D002469:Cell Separation; D018076:DNA, Complementary; D015536:Down-Regulation; D005260:Female; D005434:Flow Cytometry; D015316:Genetic Therapy / Q000379:methods*; D005822:Genetic Vectors; D007150:Immunohistochemistry; D020287:In Situ Nick-End Labeling; D018969:Insulin-Like Growth Factor Binding Proteins / Q000235:genetics* / Q000378:metabolism; D008545:Melanoma / Q000235:genetics / Q000378:metabolism / Q000628:therapy*; D051379:Mice; D008810:Mice, Inbred C57BL; D018613:Microscopy, Confocal; D010957:Plasmids; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014162:Transfection; D042461:Vascular Endothelial Growth Factor A / Q000096:biosynthesis / Q000187:drug effects*; D023041:Xenograft Model Antitumor Assays
D019496:Cancer Vaccines; D018076:DNA, Complementary; D018969:Insulin-Like Growth Factor Binding Proteins; D042461:Vascular Endothelial Growth Factor A; C102529:insulin-like growth factor binding protein-related protein 1; D053148:Caspase 3