scholarly journals B7-H3 Promotes Prostate Cancer Progression in Mice by Antagonizing Myeloid-Derived Suppressor Cell Apoptosis

2020 ◽  
Vol 19 ◽  
pp. 153303382097164
Author(s):  
Yunfen Zhou ◽  
Guangbo Zhang ◽  
Weijie Zhang ◽  
Xuedong Wei ◽  
Jianquan Hou ◽  
...  

Background: B7-H3 is an important immunomodulatory molecule, and clinical studies have confirmed that its expression level is closely correlated with prostate cancer prognosis. However, the mechanism of its biological action is unclear. Methods: An engineered cell line overexpressing B7-H3 was constructed. Cell apoptosis, growth and proliferation assays in vitro and an animal model in vivo were performed to analyze the role and possible mechanism of B7-H3 in promoting prostate cancer progression. Results: Compared with the control cell line (Mock-RM-1), the B7-H3-overexpressing prostate cancer cell line (B7-H3-RM-1) showed no significant growth differences in vitro, whereas the in vivo tumorigenesis rate of B7-H3-RM-1 was significantly higher than that of Mock-RM-1. These results suggest that B7-H3indirectly, rather than directly, promotes prostate cancer progression. Further analysis revealed that significantly higher levels of myeloid-derived suppressor cells (MDSCs) accumulated in vivo in B7-H3-RM-1 tumor-bearing mice than in Mock-RM-1 mice. In vitro and in vivo experiments showed that B7-H3-RM-1 cells significantly antagonized MDSC apoptosis. To further confirm the role of MDSCs in B7-H3-mediated prostate cancer progression, model mice were pretreated with cyclophosphamide before inoculation to clear immune cells and achieve myelo suppression. The results showed no significant differences in tumor growth between the B7-H3-RM-1 group and the Mock-RM-1 group. Conclusions: We found, for the first time, that B7-H3 can antagonize MDSC apoptosis, leading to MDSC accumulation in the tumor microenvironment and thereby promoting prostate cancer progression.

2010 ◽  
Vol 12 (3) ◽  
pp. 390-399 ◽  
Author(s):  
Xian-Qing Zhang ◽  
Xiao-Feng Huang ◽  
Shi-Jie Mu ◽  
Qun-Xing An ◽  
Ai-Jun Xia ◽  
...  

Author(s):  
Feng Yu ◽  
Yuanyuan Lin ◽  
Xinping Xu ◽  
Weipeng Liu ◽  
Dan Tang ◽  
...  

2010 ◽  
Vol 101 (10) ◽  
pp. 2234-2240 ◽  
Author(s):  
Pornsiri Pitchakarn ◽  
Kumiko Ogawa ◽  
Shugo Suzuki ◽  
Satoru Takahashi ◽  
Makoto Asamoto ◽  
...  

2018 ◽  
Author(s):  
Joseph B. Black ◽  
Hamsa Thayele Purayil ◽  
Iqbal Mahmud ◽  
Daiqing Liao ◽  
Yehia Daaka

Pharmaceutics ◽  
2021 ◽  
Vol 13 (11) ◽  
pp. 1741
Author(s):  
Mohamed A. Ali ◽  
Magdy I. Mohamed ◽  
Mohamed A. Megahed ◽  
Tamer M. Abdelghany ◽  
Khalid M. El-Say

Critical adverse effects and frequent administration, three times per day, limit the use of flutamide (FLT) as a chemotherapeutic agent in the treatment of prostate cancer. Therefore, our research aimed to develop new cholesterol-based nanovesicles for delivering FLT to malignant cells in an endeavor to maximize its therapeutic efficacy and minimize undesired adverse effects. Draper–Lin small composite design was used to optimize the critical quality attributes of FLT-loaded niosomes and ensure the desired product quality. The influence of the selected four independent variables on mean particle size (Y1), zeta potential (Y2), drug entrapment efficiency (Y3), and the cumulative drug release after 24 h (Y4) was examined. The optimized nanovesicles were assessed for their in vitro cytotoxicity, ex-vivo absorption via freshly excised rabbit intestine as well as in vivo pharmacokinetics on male rats. TEM confirmed nanovescicles’ spherical shape with bilayer structure. Values of dependent variables were 748.6 nm, −48.60 mV, 72.8% and 72.2% for Y1, Y2, Y3 and Y4, respectively. The optimized FLT-loaded niosomes exerted high cytotoxic efficacy against human prostate cancer cell line (PC-3) with an IC50 value of 0.64 ± 0.04 µg/mL whilst, it was 1.88 ± 0.16 µg/mL for free FLT. Moreover, the IC50 values on breast cancer cell line (MCF-7) were 0.27 ± 0.07 µg/mL and 4.07 ± 0.74 µg/mL for FLT-loaded niosomes and free FLT, respectively. The permeation of the optimized FLT-loaded niosomes through the rabbit intestine showed an enhancement ratio of about 1.5 times that of the free FLT suspension. In vivo pharmacokinetic study displayed an improvement in oral bioavailability of the optimized niosomal formulation with AUC and Cmax values of 741.583 ± 33.557 μg/mL × min and 6.950 ± 0.45 μg/mL compared to 364.536 ± 45.215 μg/mL × min and 2.650 ± 0.55 μg/mL for the oral FLT suspension. With these promising findings, we conclude that encapsulation of FLT in cholesterol-loaded nanovesicles enhanced its anticancer activity and oral bioavailability which endorse its use in the management of prostate cancer.


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