HIGH THROUGHPUT DRUG SCREENING OF SMALL MOLECULES TARGETING ADENOID CYSTIC CARCINOMA FROM THE SALIVARY GLANDS

Abstract

Objective The objective of this study was to tackle the current lack of effective drugs capable of managing adenoid cystic carcinomas (ACC) tumor progression. We also aim to identify new drugs capable of working effectively in combination with cisplatin in targeting ACC tumor cells. Study Design UM-ACC-2A cell line was seeded using a robotic liquid handler system (Opentrons) and cultured in two 96-well plates. Changes in cell viability and morphology were analyzed 24 hrs after adding drugs using a high-content imaging system (ImageXpress). Aiming at changes associated with epithelial-mesenchyme transition (EMT), we used SNAIL antibody while using H3 acetylated at lysine 9 as indicative of epigenetic modifications. Results We identified a pool of drugs capable of reducing ACC tumor cell viability; however, we also observed that other small molecules enhanced EMT. Of particular interest, we have identified a small pool of drugs that, when used in combination with cisplatin, reduced tumor viability and reversed the EMT phenotype. Conclusion Using a drug library in combination with cisplatin, we effectively reduced ACC tumor viability while reversing EMT. Altogether, we have identified novel drugs that hold the promise for new therapeutic strategies to manage ACC tumors from the salivary glands. The objective of this study was to tackle the current lack of effective drugs capable of managing adenoid cystic carcinomas (ACC) tumor progression. We also aim to identify new drugs capable of working effectively in combination with cisplatin in targeting ACC tumor cells. UM-ACC-2A cell line was seeded using a robotic liquid handler system (Opentrons) and cultured in two 96-well plates. Changes in cell viability and morphology were analyzed 24 hrs after adding drugs using a high-content imaging system (ImageXpress). Aiming at changes associated with epithelial-mesenchyme transition (EMT), we used SNAIL antibody while using H3 acetylated at lysine 9 as indicative of epigenetic modifications. We identified a pool of drugs capable of reducing ACC tumor cell viability; however, we also observed that other small molecules enhanced EMT. Of particular interest, we have identified a small pool of drugs that, when used in combination with cisplatin, reduced tumor viability and reversed the EMT phenotype. Using a drug library in combination with cisplatin, we effectively reduced ACC tumor viability while reversing EMT. Altogether, we have identified novel drugs that hold the promise for new therapeutic strategies to manage ACC tumors from the salivary glands.