OP-18 - SQSTM1/p62 might be involved in radio-sensitivity of HPV-infected cervical cancer cells

Abstract

Most cervical cancers are caused by human papillomavirus (HPV) infection. There have been several reports for the association between HPV infection and p62 expression. However, an adjuvant therapy targeting p62 has not been established. This study was conducted to clarify the possibility for enhancing the radio-sensitivity in cervical cancers by the p62-target therapy. We evaluated the expressions of autophagy relative proteins (p62, p-p62, LC3) in HeLa cells (HPV type 18), ME180 (HPV type 68) and C33A (HPV negative) by immunohistochemistry and western blotting. Survival after irradiation was evaluated by WST-1. We also examined the alternations of radio-sensitivity by p62 knockdown or chemical autophagy inhibitors. The expression of p62 was stronger in the cervical cancer tissues, compared to CIN. The p62 expression level was significantly higher in the HPV-positive cell lines, compared to the HPV-negative cell. Addition of CQ did not result in increased expression of p62. The expression of p62 was higher in the HPV-positive cells than that in the HPV-negative cells in the presence of Baf. Baf also increased the expression of phosphorylated p62 in the cells regardless of HPV infection. Addition of Baf increased radiosensitivity in all cells. In contrast, the addition of CQ did not affect radio-sensitivity in HPV-positive cell lines. Finally, p62 knockdown eliminated the radio-sensitivity in ME180 cells. p62 can be associated with radio-sensitivity of cervical cancer, and some autophagy inhibitors may be useful for the adjuvant therapy to increase the radio-sensitivity.