Lentivirus-mediated RNA interference targeting the ObR gene in human breast cancer MCF-7 cells in a nude mouse xenograft model.
BACKGROUND
There is a significant association between obesity and breast cancer, which is possibly due to the expression of leptin. Therefore, it is important to clarify the role of leptin/ObR (leptin receptor) signaling during the progression of human breast cancer.


METHODS
Nude mice with xenografts of MCF-7 human breast cancer cells were administered recombinant human leptin subcutaneous via injection around the tumor site. Mice in the experimental group were intratumorally injected with ObR-RNAi-lentivirus, while negative control group mice were injected with the same dose of negative-lentivirus. Tumor size was blindly measured every other day, and mRNA and protein expression levels of ObR, estrogen receptor a (ERa), and vascular endothelial growth factor (VEGF) for each group were determined.


RESULTS
Knockdown of ObR-treated xenografted nude mice with a high leptin microenvironment was successfully established. Local injection of ObR-RNAi-lentivirus significantly suppressed the established tumor growth in nude mice. ObR level was significantly lower in the experimental group than in the negative control group, while the amounts of ERa and VEGF expression were significantly lower in the leptin group than in the control group (P < 0.01 for all).


CONCLUSIONS
Inhibition of leptin/ObR signaling is essential to breast cancer proliferation and possible crosstalk between ObR and ERa, and VEGF, and may lead to novel therapeutic treatments aiming at targeting ObR in breast cancers.
Department of General Surgery, Beijing Friendship Hospital, Capital Medical University, Beijing 100050, China.
Rong-Quan
RQ
Xue
Jun-Chao
JC
Gu
Song-Tao
ST
DU
We
W
Yu
Yu
Y
Wang
Zhong-Tao
ZT
Zhang
Zhi-Gang
ZG
Bai
Xue-Mei
XM
Ma
D000818:Animals; D001943:Breast Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000628:therapy*; D047628:Estrogen Receptor alpha / Q000235:genetics / Q000378:metabolism; D005260:Female; D006801:Humans; D016086:Lentivirus / Q000235:genetics*; D061986:MCF-7 Cells; D051379:Mice; D008819:Mice, Nude; D034622:RNA Interference / Q000502:physiology; D054411:Receptors, Leptin / Q000235:genetics* / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
D047628:Estrogen Receptor alpha; D054411:Receptors, Leptin; D042461:Vascular Endothelial Growth Factor A