Overexpressed
epidermal growth factor receptor (EGFR) and overactivated epithelial-mesenchymal transition (EMT) in
triple-negative breast cancer (TNBC) can enhance
tumorigenesis and
tumor recurrence and
metastasis.
Caffeic acid p-nitro-phenethyl
ester (CAPE-pNO2) has various pharmacological activities in our previous research, but its effect on
metastasis and growth of TNBC has not been studied. In this study,
Caffeic acid phenethyl ester (CAPE) was as a positive control. in vitro, MTT, Transwell, wound healing, colony formation and cell adhesion assays were performed to examine the effect on viability, invasion, migration, colony formation and adhesion of MDA-MB-231 cells by CAPE-pNO2, the results indicated that CAPE-pNO2 significantly dose-dependently inhibited
metastasis of MDA-MB-231 cells (p < 0.05). in vivo, TNBC xenograft mice were established by subcutaneously injected with MDA-MB-231 cells, and they were used to estimate the effect on
metastasis and growth of CAPE-pNO2 after 38 days of treatment. HE staining and TUNEL staining were carried out in
tumor tissues, results showed that CAPE-pNO2 obviously suppressed the
tumor growth, induced cells apoptosis (p < 0.01) and decreased pulmonary and splenic metastatic
tumor cells. The results of IHC demonstrated that the VEGFA and Ki-67
proteins expression were downregulated (p < 0.01) in
tumor tissues. Furthermore, western blot analysis was used to quantify key
metastasis- and growth-associated
proteins expression in vitro and in vivo, the results suggested that CAPE-pNO2 downregulated the
proteins expression of p-EGFR, p-STAT3, p-Akt, MMP-2, MMP-9,
Survivin, and key EMT-related
proteins (
Vimentin and
N-cadherin) (p < 0.01), and increased the expression of
E-cadherin (p < 0.01) in vivo and in vitro. Besides, CAPE-pNO2 had a similar effect as
erlotinib in regulating the EGFR downstream
proteins in
EGF-induced MDA-MB-231cells. Collectively, these results indicated that CAPE-pNO2 possessed inhibitory effect on the growth and
metastasis of TNBC may via the EGFR/STAT3/Akt/
E-cadherin signaling pathway, and CAPE-pNO2 is better than CAPE in inhibiting growth and
metastasis.