Cytotoxic effect of gamma-delta t cells in pamidronate treated cervical cancer cells : development of a model for immunotherapy

Abstract

Cervical cancer is the second most common cancer found in women worldwide. It is a seriously public health problem, especially in recurrence and metastasis patients. The etiology of cervical cancer is caused by HPV infection. To understand the pathogenesis of HPV infection and cervical cancer and develop new approaches for cervical cancer treatment, the suitable of animal model is needed. Therefore, this study aims to develop a new mouse model for cells immunotherapy testing. The results indicated that the minimal amount of HeLa cells that could induce tumor in mouse was 2.5×105. The average of tumor size in each implanted mouse were significantly correlated with the increasing number of implanted HeLa cells (R2 = 0.98, y = 0.1171x+4.35). HPV DNA in tumor section was confirmed by using PCR, in situ hybridization with specific HPV DNA probes, and typing with HPV DNA typing kit. The result indicated the tumor was originated from HeLa cells. The killing efficacy of cells was indicated that these cells have abilities to kill all tested cervical cancer cells in vitro. The killing efficacy increased in pamidronate treated cervical cancer cells. The most sensitive cell was HeLa cell followed by SiHa, CaSki and NTY respectively. Moreover, this result indicated cells had less effect to autologous PHA blast PBMC. The killing mechanism of cells involved with degranulation of perforin and granzyme pathway. Further investigation the role of cells in developed mouse model demonstrated that these cells could deposit within tumor area and were able to induce apoptosis in tumor cells. This study was the first evidence indicating that cells could kill cervical cancer both in vitro and in vivo. Therefore, the development of cervical cancer immunotherapy in the future by using of cells could be possible.