Experimental study of the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment
10.3760/cma.j.issn.0254-5098.2020.08.001
- VernacularTitle:核素 125I标记hTERT/PSA启动子双调控溶瘤腺病毒对前列腺癌靶向治疗及肿瘤微环境的影响
- Author:
Zhenduo SHI
1
;
Zhenning WEI
;
Lin HAO
;
Kun PANG
;
Jiahe ZHOU
;
Bingzheng DONG
;
Zhiguo ZHANG
;
Yan ZHAO
;
Yufeng SUN
;
Conghui HAN
Author Information
1. 徐州市中心医院泌尿外科 徐州医科大学徐州临床学院 东南大学医学院附属徐州医院 221009
- From:
Chinese Journal of Radiological Medicine and Protection
2020;40(8):573-581
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment. Methods:125I-RSOAds-hTERT/PSA ( 125I-virus complex) oncolytic adenovirus was constructed by PCR amplification and double restriction enzyme ligation. TUNEL staining, flow cytometry and Caspase-3 immunoblotting assay were used to detect the killing effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells in vitro and in vivo, respectively. To explore the effect of 125I-virus complex on tumor tissue cytokine secretion levels, interleukin 2 (IL-2), IL-10, tumor necrosis factor-α (TNF-α) and interferon-γ (IFN-γ) in the culture supernatant of human prostate cancer cell line PC3, mouse prostate adenocarcinoma cell line RM-1, and mice serum were detected by ELISA. We explored the regulation of 125I-virus complex on the expression of CD24, CD44 and prostate stem cell antigen (PSCA) in prostate tumor tissues and tumor cells through immunohistochemistry. Meanwhile, the expression levels of CD32 and vascular endothelial growth factor (VEGF), as well as CD4+ , CD8+ and macrophage infiltration in tumor tissue were detected through immunofluorescence experiments. Results:125I-virus complex oncolytic adenovirus significantly increased tumor cell apoptosis in vitro and in vivo that was significantly higher than that of 125I group and virus complex group. Meanwhile, IL-2 ( t=-183.30, -38.20, P<0.05), IL-10 ( t=113.80, 92.71, P<0.05), TNF-α ( t=-73.20, -73.91, P<0.05), IFN-γ ( t=-65.37, -139.70, P<0.05) increased in vitro and in vivo. 125I-virus complex reduced the expression of CD24, CD44 and PSCA in tumor cells and tumor tissue, reduced the weight of tumor tissue, inhibited angiogenesis of tumor tissue ( t=8.55, P<0.05), and regulated the immune response in tumor tissue. Conclusions:125I-virus complex targeting prostate cancer can significantly kill cancer cells, reduce the weight and angiogenesis of tumor, and improve tumor microenvironment.
