Ovarian cancer patients treated with
cisplatin-based
chemotherapy often develop acquired
cisplatin resistance and, consequently,
cancer recurrence. We have previously reported that
annexin A11 is associated with
cisplatin resistance and related to
tumor recurrence in
ovarian cancer patients. In this study, we used
small interfering RNA to suppress
annexin A11 expression in
ovarian cancer cells followed by various in vitro assays. We showed that knockdown of
annexin A11 expression reduced cell proliferation and colony formation ability of
ovarian cancer cells. Epigenetic silencing of
annexin A11 conferred
cisplatin resistance to
ovarian cancer cells. Through a comprehensive time course study of
cisplatin response in
ovarian cancer cells with/without suppression of
annexin A11 expression using whole-genome
oligonucleotide microarrays, we identified a set of differentially expressed genes associated with
annexin A11 expression and some patterns of gene expressions in response to
cisplatin exposure. These identified genes/patterns were further validated by real-time polymerase chain reaction and immunoblot analysis. Many of them such as HMOX1, TGFBI, LY6D, S100P, EIF4EBP2, DHRS2, and PCSK9 have been involved in apoptosis, cell cycling/proliferation, cell adhesion/migration, transcription regulation, and signal transduction. In addition, immunohistochemistry analyses indicated that
annexin A11 immunointensity inversely correlated with HMOX1 immunoreactivity in 142
ovarian cancer patients. In contrast to
annexin A11, HMOX1 immunoreactivity positively correlated with in vitro
cisplatin resistance in
ovarian cancers. Collectively,
annexin A11 is directly involved in cell proliferation and
cisplatin resistance of
ovarian cancer. Manipulation of
annexin A11 and its associated genes may represent a novel therapeutic strategy in human
ovarian cancers.