Study Of The Arsenic Trioxide Treatment Against HPV Positive Cervical Cancer And The Progression Of Cervical Cancer

Carcinoma of the cervix is one of the most common malignancies in women,second most common malignancy in both incidence and mortality. There is a bigfinancial and laborious burden for cervical cancer screening and treatment everyyear. Highly pathogenic human papillomavirus (HPV) is closely associated withprogression of cervical cancer. Continous infection of HPV interfering with cellulargrowth regulatory proteins contributes to malignant transformation of cells. Ittakes almost ten years for cervical epithelium to develop from HPV infection tocervical intraepithelial neoplasia and ultimate cervical cancer. Cervical cancer canbe treated and prevented if we can take full use of the period during theprogression of cervical cancer. A satisfying therapeutic reagent for cervicalcancers should elinimate the continuous effects of HPV, as well as correcting thedefect gene expression in cancer cells.As₂O₃ has been indicated as a broad-spectrum anticancer medicine andsuccessfully employed in the treatment of acute promyelocytic leukemia (APL).Here we aim to show the promising future of As₂O₃ as a satisfying therapeuticreagent in cervical cancer treatment and the understanding of the mechanisms ofAs₂O₃ action. Study of cell features and tumor mouse model by As₂O₃demonstrates that As₂O₃ has a therapeutic effect on cervical cancer in vitro and invivo. In the present study, we show that As₂O₃ can induce cervical cancer cellsapoptosis through the mitochondrial pathway by downregulating expression ofHPV E6/E7 and activating JNK/p38/GADD45 and p53 signal pathways; As₂O₃ can also inhibit attachment of tumor cells to Fibronectin and Matrigel, reduce cellmotility and inhibit tumor invasion potential. In our exeriment, we also designedto evaluate the potential of As₂O₃ to inhibit the induction of malignanttransformation of TPA-immortalized and HPV-positive cervical epithelial cells invitro and in vivo (TPA is a potent tumor-promoting compound.). In our study, As₂O₃appears to decrease the risk of developing pre-invasive and invasivemalignancies in cervical epithelial cells. Our studies enlarged the range of As₂O₃usage in cervical cancer treatment and prevention, suggesting a potential clinicalapplication in cervical cancer therapies.