101P Potential immune-oncological effect of liposomal-doxorubicin in breast cancer via tumor microenvironment alteration

After invasive ductal carcinoma, invasive lobular carcinoma (ILC) is the most frequent breast cancer and accounts for nearly 15% of all breast cancers (BC). Doxorubicin (DXR) is a very effective chemotherapeutic drug utilized to treat BC but induces drug resistance and severe side effects. Recently, liposomes have gained popularity as effective tumor microenvironment (TME) modulatory anticancer agents for various malignancies, including BC. This study propose a liposomal-DXR combination to produce an immune-responsive regulatory effect on competing endogenous RNAs (ceRNAs) through alteration in TME and investigate the immunological and anticancer impact of liposomal-DXR combination via regulation of ceRNAs and immune regulatory cytokines at BC cells. MDA-MB cells were treated with varying concentration of liposomal-DXR combination and dose response curve was calculated. Total RNA was extracted and quantified by qRT-PCR and TNF-α ELISA kit. Computational target interaction was analyzed. Treatment resulted in a dose and time-dependent cell-viability and migration inhibition. Treatment altered the level of AKT1, ESR1, and ARID1A genes. Alteration in miR-17-5p compared to control cells indicated the alteration in ceRNAs network. TNF-α was found repressed in treated MDA-MB cells. Present study propose the mechanism of liposomal-DXR as potential TME modulatory, immunoregulatory anti-ILC agent through altering ceRNAs circuit, AKT1, ESR1, and ARID1A genes, and immune regulatory TNF-α in BC cells.