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2017 ; 8
(48
): 84248-84257
Nephropedia Template TP
gab.com Text
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Twit Text #
English Wikipedia
Anti-angiogenic and anti-tumor effects of metronomic use of novel liposomal
zoledronic acid depletes tumor-associated macrophages in triple negative breast
cancer
#MMPMID29137420
Cai XJ
; Wang Z
; Cao JW
; Ni JJ
; Xu YY
; Yao J
; Xu H
; Liu F
; Yang GY
Oncotarget
2017[Oct]; 8
(48
): 84248-84257
PMID29137420
show ga
Zoledronic acid (ZOL) has been used as an adjuvant therapy for breast cancer. It
is suggested that ZOL might be associated with inhibition of macrophages, which
in turn reduces tumor growth, metastasis and tumor angiogenesis. Moreover,
metronomic therapy can inhibit tumor angiogenesis and tumor immune cells.
Previously we developed ZOL based cationic liposomes that allowed a higher
intratumor delivery of drug compared with free ZOL in vivo. Therefore, in this
study, Asn-Gly-Arg (NGR) and PEG2000 were used as ligands to modify the surface
of liposomes (NGR-PEG-LP-ZOL) in metronomic therapy to clear the tumor-associated
macrophages (TAMs) and inhibit the formation of tumor angiogenesis, achieving the
purpose of anti-tumor growth. Our data showed that NGR-PEG-LP-ZOL metronomic
therapy has the strongest inhibitory effect on tumor growth. Further,
NGR-PEG-LP-ZOL metronomic therapy could significantly impair TAMs by inhibiting
the expression of CD206 antibody in tumor tissues, decreasing the expression of
cytokine related gene expression of TAMs, as well as reducing the percentage of
TAMs in tumor tissues. In addition, NGR-PEG-LP-ZOL metronomic therapy could
significantly inhibit the expression of tumor neovascular specific antibody CD31
and reduce the microvessel density. In conclusion, our study demonstrated that
NGR-PEG-LP-ZOL metronomic therapy could impair TAMs by inhibiting tumor
angiogenesis and enhance the antitumor effect of ZOL.