TY - JOUR
AU1 - Masoumi, Javad
AU2 - Zainodini, Nahid
AU3 - Basirjafar, Pedram
AU4 - Tavakoli, Tayyebeh
AU5 - Zandvakili, Raziyeh
AU6 - Nemati, Maryam
AU7 - Ramezani, Mahnaz
AU8 - Rezayati, Mohammad-Taghi
AU9 - Ayoobi, Fatemeh
AU1 - Khademalhosseini, Morteza
AU1 - Khorramdelazad, Hossein
AU1 - Arman, Rostamlou
AU1 - Jafarzadeh, Abdollah
AB - Apelin/APJ axis plays a critical role in cancer progression, thus its targeting inhibits tumor growth. However, blocking of Apelin/APJ axis in combination with immunotherapeutic approaches may be more effective. This study aimed to investigate the effects of APJ antagonist ML221 in combination with a DC vaccine on angiogenic, metastatic and apoptotic-related factors in a breast cancer (BC) model. Four groups of female BALB/c mice with 4T1-induced BC were treated with PBS, APJ antagonist ML221, DC vaccine, and “ML221 + DC vaccine”. After completion of the treatment, the mice were sacrificed and the serum levels of IL-9 and IL-35 as well as the mRNA expression of angiogenesis (including VEGF, FGF-2, and TGF-β), metastasis (including MMP-2, MMP-9, CXCR4) and apoptosis-related markers (Bcl-2, Bax, Caspase-3) in tumor tissues were determined using ELISA and real-time PCR, respectively. Angiogenesis was also evaluated by co-immunostaining of tumor tissues with CD31 and DAPI. Primary tumor metastasis to the liver was analyzed using hematoxylin–eosin staining. The efficiency of combination therapy with “ML221 + DC vaccine” was remarkably higher than single therapies in preventing liver metastasis compared to the control group. In comparison with the control group, combination therapy could significantly reduce the expression of MMP-2, MMP-9, CXCR4, VEGF, FGF-2, and TGF-β in tumor tissues (P < 0.05). It also decreased the serum level of IL-9 and IL-35 compared with the control group (P < 0.0001). Moreover, vascular density and vessel diameter were significantly reduced in the combination therapy group compared with the control group (P < 0.0001). Overall, our findings demonstrate that combination therapy using a blocker of the apelin/APJ axis and DC vaccine can be considered a promising therapeutic program in cancers.Graphical Abstract[graphic not available: see fulltext]
TI - Apelin receptor antagonist boosts dendritic cell vaccine efficacy in controlling angiogenic, metastatic and apoptotic-related factors in 4T1 breast tumor-bearing mice
JF - Medical Oncology
DO - 10.1007/s12032-023-02030-9
DA - 2023-05-15
UR - https://www.deepdyve.com/lp/springer-journals/apelin-receptor-antagonist-boosts-dendritic-cell-vaccine-efficacy-in-SH4fQLYC8k
VL - 40
IS - 6
DP - DeepDyve
ER -