Poster Presentation 25th Lorne Cancer Conference 2013

A ROLE FOR THE FREE BETA SUBUNIT OF HUMAN CHORIONIC GONADOTROPIN IN SENSITIVITY OF EPITHELIAL OVARIAN CANCER CELLS TO PLATINUM-BASED CHEMOTHERAPEUTICS (#355)

Snega S Sinnappan 1 , Xiaolang Yan 1 , Robert C Baxter 1 , Deborah J Marsh 1
  1. Kolling Institute of Medical Research, St Leonards, NSW, Australia

The beta-subunit of human chorionic gonadotropin (hCG-β) is expressed and elevated in the serum of a range of malignant tumours, including epithelial ovarian cancer (EOC). Elevated levels of hCG-β have also been associated with poor response to treatment in a number of cancers, including radiotherapy and chemotherapy. Women with EOC frequently respond to first line treatment with the platinum based chemotherapeutic drug cisplatin, but relapse when tumours develop drug resistance. We aimed to characterise the levels of hCG-β in EOC cell lines and to determine whether hCG-β has a role in the responsiveness of these cell lines to treatment with cisplatin. qRT-PCR and ELISA were used to determine endogenous levels of hCG-β in seven EOC cell lines: A2780, A2780cis (cisplatin resistant), HEY, SKOV-3, OVCAR-3, PEO-1 and OV202. All cell lines expressed hCG-β transcript and protein. SKOV-3 and HEY cells expressed the highest levels, 14 ng/ml and 3 ng/ml, respectively, and OV202, A2780, A2780cis and CaOV-3 cells expressed lower levels, ≤ 0.3 ng/ml. hCG-β was down-regulated using siRNA in HEY and A2780cis cells. Sensitivity to cisplatin and taxol was measured by the clonogenic assay. Down-regulation of hCG-β in HEY and A2780cis increased their sensitivity to cisplatin with the IC50 being four fold lower in the knockdown cells compared to control cells. The effect was not observed with taxol treatment. Interestingly, down-regulation of hCG-β also increased the sensitivity of these cells to carboplatin, another platinum-based chemotherapeutic with the IC50 being five fold lower in the knockdown cells compared to control cells. These findings suggest that hCG-β may be involved in modulating the sensitivity of some EOCs to platinum based chemotherapy and that suppression of hCG-β might be a strategy to increase the responsiveness of EOC tumours to platinum-based chemotherapy.