Document Type : Original Article
Department of Virology, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran
National Cell Bank of Iran, Pasteur Institute of Iran, Pasteur Avenue, Tehran, Iran
Shahid Modares Hospital, Shahid Beheshti University of Medical Sciences, Tehran, Iran
Objective: The human papillomavirus as an etiological agent of cervical cancer does not grow adequately in tissue culture systems. The tumor cell line TC-1 continuously expresses the E6 and E7 oncogenic proteins of HPV, and is considered a suitable tool in laboratory investigations and vaccine researches against cervical cancer.
Materials and Methods: The TC-1 cell line was grown in RPMI 1650 supplemented with 10% FBS, glutamine and antibiotics, and was used for tumor development in mice. Six to seven week-old tumor bearing C57BL/6 mice were divided into 3 groups consisting of 7 mice per group. The first group received pcDNA-E7, the second group received pcDNA3, and the third group received phosphate buffered saline (PBS). The treated animals were monitored for their tumor size progression and survival. At last, the tumoric tissues from autopsied animals were fixed and examined with Mayer's hematoxylin and eosin (H&E). All experiments were done in accordance with guidelines of the Laboratory Animal Ethical Commission of Tarbiat Modares University. Data analysis was performed using the oneway ANOVA followed by Tukey's test in both experimental and control groups. A p-value<0.05 was considered significant.
Results: There were significant decreases in tumor growth; there were also improvements in survival among mice in the treated groups (p<0.041). H&E stained sections from untreated mice were studied independently in a blinded fashion by two observers and showed malignant neoplasms composed of severely pleomorphic tumor cells with nuclear
enlargement, high nuclear-cytoplasmic (N/C) ratios, and prominent nucleoli in solid and fascicular patterns of growth. High mitotic activity with extensive necrosis was also noted in both test and control groups.
Conclusion: The TC-1 lung metastatic model can be used to test the efficacy of various E7-based therapeutic cancer vaccine strategies for cervical cancer and the prevention of HPV-related neoplasia.