A study conducted in breast cancer cells found that (valproic acid) inhibits CIP2A/C-MYC/PI3K/Akt/mTOR signaling molecules and PD-L1

Abstract

Abstract Background Resistant cells are a critical problem that reduce treatment efficacy of breast cancer. Nowadays, CIP2A and PD-L1 are considered as theraputical challenges in breast cancer, because of responsible for drug resistance and immune evasion respectively. Hence, identifying agents to suppress these factors is great of interest. Specifically, epigenetic drugs can be an effective approach to alter the behavior of genes. Objective The objective of this study is to evaluate the drug effects and molecular mechanisms of valproic acid (VPA) as a HDAC inhibitor, particularly its effect on CIP2A and PD-L1 in breast cancer MCF-7 cell line. Materials and Methods In this study, MCF-7 cells were treated with various concentration of VPA for 24 h, 48 h, and 72 h. The rate of cell viability was measured by MTT assay. Finally, gene expressions of CIP2A, c-MYC, PI3K, Akt, mTOR and PD-L1 were analyzed by real time PCR and ΔCT method. Result VPA showed a growth inhibitory effect in MCF-7 cell line. This effect is achieved by decreasing the expression levels of CIP2A oncogene and its downstream signaling molecules i.e. c-MYC, PI3K, Akt and mTOR. In addition to being a CIP2A targeting agent, VPA also inhibits PD-L1 in MCF-7 cell line. Conclusions Our findings suggest that VPA can be a novel approach to combat with challenges caused by CIP2A and PD-L1, thereby alone or in combination with existing therapies could be promising strategy to get more efficiencies in treatments for breast cancer patients.