Introduction: The beta-subunit of human chorionic gonadotropin (hCG-β) is elevated in the serum of women with a range of malignant cancers, including High Grade Serous Cancer (HGSC). Elevated levels of hCG-β have also been associated with poor response to radiotherapy and chemotherapy in some cancers. Women with HGSC frequently respond to first line treatment with the platinum based chemotherapeutic drug cisplatin, but relapse with tumours developing chemoresistance. This study aimed to characterise the levels of hCG-β in HGSC cell lines and to determine whether hCG-β has a role in the responsiveness of these cell lines to treatment with cisplatin.

Methods: qRT-PCR and ELISA were used to determine endogenous levels of hCG-β in seven HGSC cell lines. hCG-β was down-regulated using siRNA in HEY and A2780cis (cisplatin resistant) cells and their sensitivity to cisplatin was determined using  the clonogenic assay. Liquid chromatography-mass spectrometry using isobaric tags for relative and absolute quantitation (iTRAQ) was used to determine the mechanism(s) by which hCGβ may be involved in the sensitivity of HGSC cells to cisplatin. Specifically, protein was harvested from A2780cis cells with and without hCGβ downregulation plus or minus treatment with cisplatin at IC50 levels (2μg/ml) for 24h. Protein extracts were then iTRAQ-labelled and global protein changes determined.

Results: All cell lines expressed hCG-β transcript and protein at various levels. Down-regulation of hCG-β in HEY and A2780cis increased their sensitivity to cisplatin, carboplatin and oxaliplatin. iTRAQ results showed differences in proteins associated with the cell cycle, death and survival pathways, as well as DNA replication, damage and repair.

Conclusions: These findings suggest that hCG-β may be involved in modulating the sensitivity of some HGSCs to platinum based chemotheraputics. Suppression of hCG-β may be a strategy to increase the responsiveness of primary HGSCs to cisplatin.