ANLN Directly Interacts with RhoA to Promote Doxorubicin Resistance in Breast Cancer Cells

Feng Wang,* Zhen Xiang,* Teng Huang,* Min Zhang, Wei-Bing Zhou Department of Oncology, Xiangya Hospital, Central South University, Changsha, Hunan 410008, People’s Republic of China*These authors contributed equally to this workCorrespondence: Wei-Bing Zhou Department of OncologyXiangya Hospital, Central South University, No. 87 Xiangya Road, Changsha, Hunan 410008, People’s Republic of ChinaTel +86-731-89753733Email zhouweibing298@csu.edu.cnBackground: Chemotherapy resistance is the leading cause of cancer treatment failure. This research was conducted to explore a potential link between actin-binding protein anillin (ANLN) and doxorubicin resistance in breast cancer.Materials and Methods: We compared ANLN expression and 50% inhibition concentration (IC50) of doxorubicin in human breast cancer cells (MDA-MB-231) and human breast cancer cells with doxorubicin resistance (MDA-MB-231/ADM). Co-immunoprecipitation was used to investigate the interaction between ANLN and RhoA. The cell viability, apoptosis, gene and protein expression were estimated by MTT, flow cytometry, quantitative real-time PCR and western blot.Results: The doxorubicin resistance in MDA-MB-231/ADM cells (IC50 = 19.40 ± 1.16 μg/mL) was significantly higher than that in MDA-MB-231 cells (IC50 = 1.65 ± 0.23 μg/mL). ANLN was up-regulated in MDA-MB-231/ADM cells compared to MDA-MB-231 cells. Furthermore, ANLN overexpression promoted cell viability and inhibited apoptosis of MDA-MB-231 cells. The gene and protein expression of multidrug resistance (MDR1) and cancer resistance protein (BCRP) were enhanced by ANLN overexpression in MDA-MB-231 cells. ANLN silencing suppressed cell viability and the expression of MDR1 and BCRP and facilitated apoptosis in MDA-MB-231/ADM cells. Moreover, ANLN promoted RhoA activation by interacting with RhoA. ANLN up-regulation enhanced cell viability and the expression of MDR1 and BCRP and decreased apoptosis of MDA-MB-231 cells. The influence conferred by ANLN overexpression was effectively abolished by C3 ...