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| Effect of histone deacetylase inhibitor combined with HPV16E7-DNA vaccine in the treatment of cervical cancer and study on its mechanism |
| HUANG Zhuomin LI Qing YAO Xiuhua JIN Ping |
| Department of Gynecology, Shenzhen Maternity and Child Healthcare Hospital, Southern Medical University, Guangdong Province, Shenzhen 518028, China |
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Abstract Objective To investigate the effect of combination of histone deacetylase inhibitor (HDACI) Suberoylanilide Hydroxamic Acid (SAHA) combined with human papilloma virus 16 E7-DNA (HPV16E7-DNA) vaccine in the treatment of cervical cancer and its immunological mechanism. Methods The model of mice with TC-1 cervical cancer was made, then on the 5th day after tumor bearing, the mice were randomly divided into HPV16E7-DNA group, SAHA group, SAHA and HPV16E7-DNA group, control group by random number table method. The therapeutic regimen was as followed: HPV16E7-DNA group was given vaccine 5 μg/kg, SAHA group was given SAHA 20 mg/kg, SAHA and HPV16E7-DNA group was given vaccine 5 μg/kg+SAHA 20 mg/kg, the control group was given 100 μL phosphate solutions (PBS). Once every 3 days, total for 4 times. The tumor growth curve was drawn; the amount of CD8+T cells in peripheral blood of mice in each group was detected by flow cytometry; the effects of different doses of SAHA (25.0, 12.5 nmol/L) for the expression of H-2Kb of MHC class Ⅰ in TC-1 cells were detected by experiment in vitro. Results Compared with the other three groups, the tumor growth rate in SAHA and HPV16E7-DNA group was significantly slowed down, the amount of HPVE7 specific CD8+T cells in peripheral blood of mice was significantly increased (P ＜ 0.05). In-vitro experiment showed that compared with control group, the expression of H-2Kb of MHC class Ⅰ in SAHA group was increased significantly (P ＜ 0.05), while there was no significant difference between low dose of SAHA group and high dose of SAHA group (P ＞ 0.05). Conclusion HDACI combined with HPV16E7-DNA vaccine comes into significant anti-tumor effects may be through up-regulating expression of MHC class Ⅰ of the tumor cells and activating the immune response of CD8+T cells, which is expected to be used in the immunotherapy of cervical cancer.
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