Three of these cell lines formed dense aggregates or spheroids (HEY, SKOV-3, and OVCAR-8) in 3D and the treatment effect was analyzed with a multicontent readout (cytotoxicity, viability, and caspase3/7 activation). In 2D, the effect on five cell lines was analyzed with two readouts. Here, we tested the effect of the ADAM17 inhibitor GW280264X in combination with cisplatin on ovarian cancer cells in 2D and 3D. Therefore, blocking ADAM17 during chemotherapy may overcome resistance. ADAM17 can be activated by chemotherapeutics, which leads to enhanced tumor growth due to concomitant substrate cleavage. One potential therapeutic target for OvCa is A disintegrin and metalloprotease 17 (ADAM17). For this reason, we analyzed our drug combination not only in monolayers but also in three-dimensional (3D) tumor spheroids. However, many promising drug candidates tested in two-dimensional (2D) cell culture have not proved successful in the clinic. Thus, novel treatment combinations are highly warranted. Chemotherapy resistance is a major challenge in ovarian cancer (OvCa).

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