The nucleus is a key organelle in mammary cells, which is responsible for several cellular functions including cell proliferation, gene expression, and cell survival. In addition, the nucleus is the primary targets of
doxorubicin treatment. In the current study, low-abundance
nuclear proteins were enriched for proteomic analysis by using a state-of-the-art two-dimensional differential gel electrophoresis (2D-DIGE) and matrix-assisted
laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS) strategy to compare and identify the
nuclear protein profiling changes responsible for the development of
doxorubicin resistance in human
uterine cancer cells. The results of the nuclear proteomic analysis indicated that more than 2100
protein features were resolved from an equal pooled amount of three purified
nuclear proteins and 117 differentially expressed spots were identified. Of these 117 identified
proteins, 48 belonged to
nuclear proteins and a positive correlation was observed between the expression levels of 32 of these
nuclear proteins and an increase in drug resistance. According to our review of relevant research,
nuclear proteins such as DNA repair
protein XRCC3 (XRCC3) have not been reported to play roles in the formation of
doxorubicin resistance. Previous studies have used RNA interference and cell viability analysis to evidence the essential roles of XRCC3 on its potency in the formation of
doxorubicin resistance. To sum up, our nuclear proteomic approaches enabled us to identify numerous
proteins, including XRCC3, involved in various drug-resistance-forming mechanisms. Our results provide potential diagnostic markers and therapeutic candidates for treating
doxorubicin-resistant
uterine cancer.