EXPERIMENTAL STUDY ON THE EFFECT OF THE NUCLIDE 125I LABELLED PSA/HTERT PROMOTER DOUBLE-REGULATED ONCOLYTIC ADENOVIRUS ON TARGETED THERAPY AND THE MICROENVIRONMENT OF PROSTATE CANCER

Zhenduo Shi*, Lin Hao* Wen Yang**, Kun Pang*, Jiahe Zhou*, Bingzheng Dong*, Zhiguo Zhang*, Yan Zhao*, Rongsheng Zhou*, Conghui Han*, #

*Urology Surgery, Xuzhou Central Hospital, Xuzhou City, Jiangsu Province, China - **Nephrology, Affiliated Hospital of Shandong Academy of Medical Sciences

Objective: To investigate the effect of the 125I-RSOAds-hTERT/PSA oncolytic adenovirus on targeted therapy and the tumour microenvironment of prostate cancer.

Methods: An 125I-RSOAds-hTERT/PSA oncolytic adenovirus was constructed using PCR amplification and double enzymatic connection techniques. The killing effect of the 125I-RSOAds-hTERT/PSA oncolytic adenovirus on prostate cancer cells was detected by TUNEL staining, flow cytometry, and a Caspase-3 immunoblotting assay in vivo and in vitro, respectively. The secretion levels of IL-2, IL-10, TNF α, and IFN-γ in PC3 and RM-1 cell culture supernatant and serum were detected by an ELISA assay, and the effect of the 125I-RSOAds-hTERT/PSA oncolytic adenovirus on the secretion of cytokines in tumour tissues was investigated. The effects of 125I-RSOAds-hTERT/PSA oncolytic adenovirus on the expression of CD24, CD44, and PSCA in prostate adenoma tissues and tumour cells were studied using immunohistochemistry and an immunofluorescence assay. At the same time, expression of CD32 and VEGF, levels of CD4+ and CD8+, and macrophage infiltration were detected.

Results: The 125I-RSOAds-hTERT/PSA oncolytic adenovirus could induce apoptosis of tumour cells in vivo and in vitro, which was significantly higher than that in any individual nuclide 125I group and unlabelled RSOAds-hTERT/PSA group. At the same time, the secretion levels of IL-2, TNF α, IFN-γ, and other cytokines were significantly increased in vivo and in vitro, but the IL-10 secretion levels were obviously increased in vivo and significantly decreased in vitro. It has been shown that the 125I-RSOAds-hTERT/PSA oncolytic adenovirus can reduce the expression of CD24, CD44, and PSCA in tumour cells and tumour tissues, reduce the weight of tumour tissues, inhibit the angiogenesis of tumour tissues, and regulate the immune response in tumour tissues.

Conclusion: Using the 125I-RSOAds-hTERT/PSA oncolytic adenovirus for targeting prostate cancer can significantly kill cancer cells, reduce the weight of cancer tissue and angiogenesis, and improve the tumour microenvironment.