Targeting CD146 in combination with vorinostat for the treatment of ovarian cancer cells.

Drug resistance is the predominant cause of mortality in late-stage patients with ovarian cancer. Histone deacetylase inhibitors (HDACis) have emerged as a novel type of second line drug with high specificity for tumor cells, including ovarian cancer cells. However, HDACis usually exhibit relatively low potencies when used as a single agent. The majority of current clinical trials are combination strategies. These strategies are more empirical than mechanism-based applications. Previously, it was reported that the adhesion molecule cluster of differentiation 146 (CD146) is significantly induced in HDACi-treated tumor cells. The present study additionally confirmed that the induction of CD146 is a common phenomenon in vorinostat-treated ovarian cancer cells. AA98, an anti-CD146 monoclonal antibody (mAb), was used to target CD146 function. Synergistic antitumoral effects between AA98 and vorinostat were examined and . The potential effect of combined AA98 and vorinostat treatment on the protein kinase B (Akt) pathway was determined by western blotting. The present study found that targeting of CD146 substantially enhanced vorinostat-induced killing via the suppression of activation of Akt pathways in ovarian cancer cells. AA98 in combination with vorinostat significantly inhibited cell proliferation and increased apoptosis. , AA98 synergized with vorinostat to inhibit tumor growth and prolong survival in ovarian cancer. These data suggest that an undesired induction of CD146 may serve as a protective response to offset the antitumor efficacy of vorinostat. By contrast, targeting CD146 in combination with vorinostat may be exploited as a novel strategy to more effectively kill ovarian cancer cells.