Poster Presentation 32nd Lorne Cancer 2020

Role of ABCA1 transporter in high grade serous ovarian cancer progression and chemoresistance (#301)

Noor A Lokman 1 , Wanqi Wang 1 , Anne M Macpherson 1 , Martin K Oehler 1 2 , Carmela Ricciardelli 1
  1. Discipline of Obstetrics and Gynaecology, Adelaide Medical School, Robinson Research Institute, The University of Adelaide, Adelaide, SA, Australia
  2. Department of Gynaecological Oncology, Royal Adelaide Hospital, Adelaide, SA, Australia

Ovarian cancer is the leading cause of death from gynaecological malignancies. The majority of ovarian malignancies are high grade serous ovarian cancers (HGSOC) that have a high chemosensitivity to first line platinum-based therapies. However, the majority of cancers relapse and subsequently develop multidrug-chemoresistance. Several studies have provided evidence that ABC (ATP-binding cassette) transporters play important roles in chemotherapy resistance; however, there have been limited studies on HGSOC. This study investigated the relationship between ABC transporter expression, chemoresistance and HGSOC patient clinical outcome. mRNA expression of ABC transporters (ABCA1, ABCB1, ABCB3, ABCC2 and ABCG2) in HGSOC (n=1435) was investigated by analysing publicly available online databases and by qRT-PCR of serous ovarian cancer cell lines (OV-90, CAOV3) and primary serous ovarian cancer cells (chemosensitive n=11, chemoresistant n=9). Additionally, ABC transporter protein expression was examined by immunohistochemistry on patient tissues at diagnosis (n=138), post-chemotherapy (n=21) and relapse (n=5). High ABCA1 or ABCC2 mRNA expression and high ABCA1, ABCB1 or ABCG2 protein expression were significantly associated with poor outcome. ABCA1 mRNA expression was increased in chemoresistant serous ovarian cancer cell lines. Furthermore, ABCA1 protein was significantly increased by chemotherapy and following relapse. ABCB3 mRNA expression was increased in chemoresistant primary serous ovarian cancer cells compared to chemosensitive cells. These results suggest that inhibiting ABCA1 transporter may be useful in overcoming chemotherapy resistance and improving outcome for patients with HGSOC.