Lactotransferrin (LTF) has been shown to regulate tumorogenesis. However, little 
is known about the role of LTF in regulating the development of human 
nasopharyngeal carcinoma (NPC). The aim of our study was to investigate whether 
LTF could regulate the development of NPC by characterizing the pattern of LTF 
expression in human NPC tissues using cDNA and tissue microarrays. Loss of LTF 
expression was observed in a significantly higher frequency of NPC tissues 
compared to that in nontumor nasopharyngeal epithelial tissues. While 61.25% of 
NPC tissues at the T1/T2 stage were positive for LTF expression, only 40.82% of 
NPC at the T3/T4 stage were stained by anti-LTF. Similarly, 41.58% of NPC with 
local lymph node metastasis displayed LTF expression, a value significantly 
lower than the 46.36% in primary tumors (p < 0.05). These findings suggest that 
LTF may negatively regulate the development and metastasis of NPC in vivo. 
Furthermore, overexpression of or treatment with LTF inhibited the proliferation 
of NPC cells and promoted cell cycle arrest at the G(0)/G(1) phase in vitro. 
While LTF treatment downregulated expression of cyclin D1 and phosphorylation of 
retinoblastoma protein (Rb), expression of p21 and p27 in 5-8F NPC cells was 
enhanced. Moreover, LTF treatment modulated the mitogen-activated protein kinase 
(MAPK) pathway, but did not affect p53 and STAT3 expression in 5-8F NPC cells. 
Thus LTF is likely to be a candidate tumor suppressor and downregulates the 
development of NPC by inhibiting NPC proliferation through induction of cell 
cycle arrest and modulation of the MAPK signaling pathway. Therefore, our 
findings provide new insights in understanding the mechanism(s) underlying the 
action of LTF in regulating the development of human NPC.