Abstract:

Objective To explore changes in prostate cancer tumor growth following treatment with mesenchymal stem cells （MSCs） modified with Ad*Sirt1，and to analyze the possible mechanism. Methods MSCs modified with Ad-Sirt1（MSCs-Sirt1） or with Ad-GFP （MSCs-GFP） and then mixed with RM-l cells from C57BL/6 mice were subcutaneously administered into the armpit area of C57BL/6 mice in order to establish a tumor-bearing mouse model and detect tumor growth. Natural killer（NK） cells were detected in the tumor regions of the mice. Results All mice survived until they were sacrificed on day 10 after subcutaneous injection. There was no tumor formation when MSCs were injected alone，while tumor incidence was 100% for other groups. In a tumor-bearing mouse model，the relative tumor weight of prostate cancer cells pretreated with MSCs-Sirt1，MSCs-GFP or MSCs was，respectively，（0.71±0.04），（1.58±0.05） and（1.51±0.06） g. These weights were significantly different from that in the control group （1.10±0.05 g，P<0.05）. Levels of NK cells in tumor regions were dramatically higher in mice treated with MSCs-Sirt1 and RM-1 than in control mice or mice treated with MSCs-GFP or MSCs（P<0.05）. Conclusions MSCs modified with Ad-Sirt1 can effectively inhibit prostate cancer cell growth. The reason may be that NK cells accumulate in the inflammatory tumor microenvironment.

Key words: Prostate neoplasms, Transplanted tumor model, Mesenchymal stem cells, Sirt1, Natural killer cells