اثر ويروس بيماري نيوكاسل در زنان مبتلا به نئوپلازي داخل اپي‌تليال دهانه رحم

Background: Cervical cancer is one of the most common malignancies in women, and its treatment has many side effects. Therefore, in this research, the effects of the LaSota strain of oncolytic Newcastle disease virus vaccine on cervical intraepithelial neoplasia (CIN) patients were investigated. Methods: LaSota strain of Newcastle disease virus was inoculated into 9-11 days embryonated eggs and virus titer was read using agglutination test and EID50. To determine the infectious dose of the virus on HeLa, HNCF cells, plaque assay was used. In addition, the cytotoxic effects of NDV on cell lines were eva‎luated using the MTT test, and the percentage of cell apoptosis was measured using the flow cytometry technique. Also, the content of reactive oxygen species (ROS) was measured and the expression level of Bax and Bcl-2 proteins was eva‎luated using western blot technique. In clinical experiment, 15 patients who met the inclusion criteria and diagnosed as CIN II and CIN III were included in the study. The vaccine was injected inside the cervix (neoplasia site) at increasing doses during 21 days, and they were eva‎luated for adverse events. NDV antibody titer was measured in 90 days and the presence of ki-67 and p16 proteins were studied by immunohistochemistry. Also, the levels of some important inflammatory cytokines in the serum of CIN patients were measured and finally the patients were eva‎luated according to the final outcomes and the reduction of tumor lesions. Results: HeLa and CC1 cell lines exposed to high MOI of NDV showed a greater decrease in cell viability. However, the HNCF cell line did not show sensitivity to NDV. The death of cancer cells was mostly caused by the induction of apoptosis and these cells had high ROS content. Western blot analysis showed up-regulation of Bax and down-regulation of Bcl-2 in HeLa and CC1 cancer cell lines. In clinical study, only in the first dose of vaccine some patients showed flu-like symptoms. The accumulation of NDV antibodies started on the 7th day of the study and increased until the 90th day. Administration of LaSota vaccine had no significant effect on the expressions of Ki-67 and p16 proteins. Nevertheless, a decrease in the serum levels of Il-1β was observed in patients after the administration of the vaccine, but the serum levels of both Il-2 and IFN-γ upregulated significantly. Also, vaccine administration had no significant effect in reducing CIN grades and lesions. Conclusions: Even though the cytotoxic effects of LaSota strain of NDV were seen on HeLa and CC1 cell lines, in clinical section, we concluded that LaSota strain of NDV vaccine has no therapeutic effectiveness in CIN patients.

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