Here we targeted mDia formins, cytoskeletal regulators that impact EOC invasion, in combination with standard of care EOC chemotherapy drugs including taxol or cisplatin.
We found that SMIFH2-mediated mDia formin inhibition significantly reduced both ES2 and Skov3 monolayer viability, while spheroid viability was minimally impacted only at the highest concentrations.
Combining either cisplatin or taxol with SMIFH2 did not significantly enhance the effects of either drug alone in ES2 monolayers, while Skov3 monolayers treated with taxol or cisplatin with SMIFH2 showed significant additive effects upon inhibition of viability. Interestingly, when we treated EOC spheroids with combined therapy, ES2 spheroids were highly responsive to dual taxol or cisplatin with SMIFH2 treatments, with clear additive effects observed upon viability.
In contrast, combined taxol with SMIFH2 treatment of Skov3 spheroids also showed additive effects relative to single treatments, yet Skov3 spheroids showed no additive effects from combined cisplatin and SMIFH2 treatments