Ultrasound boosts doxorubicin efficacy against sensitive and resistant ovarian cancer cells

: Ovarian cancer (OC) is characterised by the highest mortality of all gynaecological malignancies, frequent relapses, and the development of resistance to drug therapy. Sonodynamic therapy (SDT) is an innovative anticancer approach that combines a chemical/drug (sonosensitizer) with low-intensity ultrasound (US), which are both harmless per sé, with the sonosensitizer being acoustically activated, thus yielding localized cytotoxicity often via reactive oxygen species (ROS) generation. Doxorubicin (Doxo) is a potent chemotherapeutic drug that has also been recommended as a first-line treatment against OC. This research work aims to investigate whether Doxo can be used at very low concentrations, in order to avoid its significant side effects, as a sonosensitiser under US exposure to promote cancer cell death in Doxo non-resistant (A2780/WT) and Doxo resistant (A2780/ADR) human OC cell lines. Moreover, since recurrence is an important issue in OC, we have also investigated whether the proposed SDT with Doxo induces immunogenic cell death (ICD) and thus hinders OC recurrence. Our results show that the sonodynamic anticancer approach with Doxo is effective in both A2780/WT and A2780/ADR cell lines, and that it proceeds via a ROS-dependent mechanism of action and immune sensitization that is based on the activation of the ICD pathway.