Abstract:

Objective To investigate the inhibition effects of CpG oligodeoxynucleotide (CpG ODN) on renal carcinoma cell proliferation and tumor growth in vivo and in vitro, and explore the possible mechanism. Methods The effects of different concentrations of CpG ODN1826 and non-CpG ODN1982 (ODN1982) interventions on proliferation of human renal clear cell carcinoma cell line Caki-1 cultured in vitro were determined with CCK-8 method. Tumor-bearing nude mouse models were established by subcutaneous implantation of Caki-1 cells into 24 BALB/c mice, and were randomly divided into control group (PBS), ODN1982 group (50 μg ODN1982), low-dose CpG ODN1826 group (25 μg CpG ODN1826) and high-dose CpG ODN1826 group (50 μg CpG ODN1826) 4 d later according to means of weekly treatment, with 6 mice in each group. Mice were sacrificed 35 d after model establishment, and changes of tumor volumes, tumor weight and tumor histology were compared among groups. Splenic lymphocytes of tumor-bearing mice in each group were isolated in vitro, and lactate dehydrogenase release method was employed to detect the cytolytic activity of splenic lymphocytes of tumor-bearing mice to tumor cells with different effector/target ratios (splenic lymphocytes∶Caki-1 cells or splenic lymphocytes∶YAC-1 cells). Results ODN1982 had no significant effect on in vitro proliferation of Caki-1 cells, while 500 μg/mL CpG ODN1826 significantly inhibited proliferation of Caki-1 cells. The tumor volumes of low-dose CpG ODN1826 group and high-dose CpG ODN1826 group were significantly smaller than those of control group and ODN1982 group at the end point of experiment （P<0.05）, and there were significant differences in tumor weight among groups (P＜0.05). It was revealed by histological observations that there were more inflammatory cell infiltration in low-dose CpG ODN1826 group and high-dose CpG ODN1826 group. The cytolytic activity of splenic lymphocytes of mice in high-dose CpG ODN1826 group to Caki-1 cells and YAC-1 cells was (9.74±1.16)% and (79.65±5.23)%, respectively at effector/target ratio of 50∶1, and was significantly higher than that in control group [(7.67±0.22)% and (10.12±3.03)%, respectively] and ODN1982 group [(7.66±0.93)% and (27.60±9.83)%, respectively] (P<0.05). Conclusion CpG ODN can inhibit renal carcinoma cell proliferation in vitro and tumor growth in tumor-bearing nude mice, and the mechanism may relate to the enhancement of innate immunity by CpG ODN.

Key words: CpG oligodeoxynucleotide, renal carcinoma, innate immunity