| Shi Zhenduo,Wei Zhenning,Hao Lin,et al.Experimental study of the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment[J].Chinese Journal of Radiological Medicine and Protection,2020,40(8):573-581 |
| Experimental study of the effect of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy of prostate cancer and its effect on tumor microenvironment |
| Received:November 12, 2019 |
| DOI：10.3760/cma.j.issn.0254-5098.2020.08.001 |
| KeyWords:125I hTERT/PSA promoter dual regulation Oncolytic adenovirus Prostate cancer Targeted therapy |
| FundProject:江苏省社会发展重点项目（BE2019637、BE2017635）；江苏省医学创新团队（CXTD-2017048）；江苏省青年医学人才（QNRC2016386）；国家自然科学基金面上项目（81774089，81502387）；江苏省高等学校自然科学研究面上项目（17KJB360001） |
| Author Name | Affiliation | E-mail | | Shi Zhenduo | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Wei Zhenning | School of Medicine, Jiangsu University, Zhenjiang 212013, China | | | Hao Lin | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Pang Kun | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Zhou Jiahe | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Dong Bingzheng | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Zhang Zhiguo | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Zhao Yan | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Sun Yufeng | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | | | Han Conghui | Department of Urology Surgery, Xuzhou Central Hospital, Xuzhou Clinical School of Xuzhou Medical University, Xuzhou Central Hospital Affiliated to Medical School of Southeast University, Xuzhou 221009, China | Hanchdoctor@qq.com |
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| 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. |
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