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2017 ; 14
(4
): 4078-4084
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Zoledronic acid inhibits infiltration of tumor-associated macrophages and
angiogenesis following transcatheter arterial chemoembolization in rat
hepatocellular carcinoma models
#MMPMID28943915
Zhou DY
; Qin J
; Huang J
; Wang F
; Xu GP
; Lv YT
; Zhang JB
; Shen LM
Oncol Lett
2017[Oct]; 14
(4
): 4078-4084
PMID28943915
show ga
Hepatic transcatheter arterial chemoembolization (TACE), a minimally invasive
procedure to block the blood supply of tumors and release of cytotoxic agents, is
preferentially applied to patients with hepatocellular carcinoma (HCC) who are
not able to receive radical treatments. However, the long-term effects of TACE
are unsatisfactory, as the microenvironment following procedure stimulates tumor
angiogenesis, which promotes recurrence and metastasis of residual tumors. Tumor
associated macrophages (TAMs) have been revealed to stimulate tumor growth and
angiogenesis associated with poor prognosis in HCC. The present study focused on
the changes in TAMs following TACE, and explored the effects of TACE in
combination with the TAM inhibitor zoledronic acid (ZA) in rat HCC models.
Orthotropic HCC rats were divided into three groups: Sham TACE, TACE alone and
TACE combined with ZA treatment. At 7 or 14 days following TACE, tumor growth was
evaluated by magnetic resonance imaging (MRI). Infiltration of TAMs was assessed
by histological analysis and flow cytometry. Tumor angiogenesis was measured as
the mean vessel density, and initial slope was calculated from dynamic contrast
enhancement MRI. Local and systemic levels of vascular endothelial growth factor
(VEGF) were determined by western blotting or an ELISA, respectively. The results
revealed that TACE inhibited tumor growth at 7 days following the procedure, but
this inhibition was attenuated at 14 days following the procedure compared with
the sham TACE control. If combined with ZA treatment, TACE exhibited a stable
inhibition effect on tumor growth until the end of observation. Investigation of
the underlying mechanisms demonstrated that TACE combined with ZA treatment
inhibited infiltration of F4/80 positive TAMs and tumor angiogenesis compared
with the TACE alone group at 14 days following the procedure. Additionally, the
combination treatment significantly inhibited secretion of VEGF in the present
models. In conclusion, ZA treatment enhanced the effects of TACE through
inhibiting TAM infiltration and tumor angiogenesis in rat HCC models.