The up-regulation of PAK2 indicates unfavorable prognosis in patients with serous epithelial ovarian cancer and contributes to paclitaxel resistance in ovarian cancer cells.

Abstract

Abstract The main challenge in the treatment of ovarian cancer has been the development of resistance to chemotherapy. Previous studies have reported over-expression of PAK2 in various cancers through different mechanisms. The objective of this study was to investigate whether up-regulation of PAK2 contributes to chemo-resistance and poor prognosis in ovarian cancer. Bioinformatics analysis was initially employed and revealed a significant up-regulation of PAK2 in ovarian malignant tumors compared to adjacent tissues, particularly in patients with stage III-IV disease compared to those with stage I-II disease (P = 0.0056). High expression of PAK2 was associated with decreased OS, but not DFS, in ovarian cancer patients. Immunohistochemistry demonstrated positive expression of PAK2 in chemo-resistant serous EOC tissues, predominantly localized in the cytoplasm, which correlated with poor OS and DFS. In vitro studies indicated that inhibition of PAK2 expression in A2780/Taxol cells resulted in reduced colony formation, increased apoptosis, and impaired cell migration. Finally, RNA Binding Protein Immunoprecipitation (RIP) Assay and luciferase reporter assays were employed which confirmed that lnc-SNHG1 acts as a competing endogenous RNA (ceRNA) by binding to miR-216b-5p and subsequently modulating the expression of PAK2. In conclusion, our study confirmed that PAK2 may serve as a predictive marker for chemo-resistance and poor prognosis in ovarian cancer and could potentially be targeted therapeutically to overcome chemo-resistance.