Abstract. The aim of this study was to investigate the effects of emodin on the proliferation of human breast cancer cells . Cell viability following emodin treatment was assessed by 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The effects of emodin on apoptosis were determined by flow cytometry using Annexin V-fluorescein isothiocyanate and propidium iodide staining. Quantitative polymerase chain reaction and western blot analysis were used to determine changes in the expression of apoptotic genes and protein, respectively. The effect of emodin on the invasiveness of breast cancer cells was evaluated by Matrigel invasion assay. Treatment of breast cancer cells Bcap-37 and ZR-75-30 with emodin was observed to inhibit the growth and induced apoptosis in a time-and dose-dependent manner. Emodin reduced the level of Bcl-2 and increased levels of cleaved caspase-3, PARP, p53 and Bax. These findings indicate that emodin induces growth inhibition and apoptosis in human breast cancer cells. Emodin may be a potential therapeutic agent for the treatment of breast cancer. IntroductionBreast cancer is a common malignant tumor and accounts for the majority of cancer mortality in females (1). Breast cancer has an estimated incidence of 1,676,633 and had an estimated mortality rate of 521,817 in 2012 worldwide (2). In China, there has been an increasing incidence of breast cancer in recent decades (3). In 2012, it was estimated that ~48,000 females would succumb to breast cancer. To date, chemotherapy has been the mainstay for the treatment of breast cancer. However, the side effects and drug resistance associated with chemotherapy have limited its effectiveness for the treatment of breast cancer (4,5). A number of natural extractions have demonstrated a wide range of biological activity and low toxicity in animal models, and have been considered as an alternative method of breast cancer treatment (6,7).Emodin (1,3,8-trihydroxy-6-methylanthraquinone) is a biologically active anthraquinone identified in the roots and bark of a number of plants. Emodin is also observed naturally in a number of widely used Chinese medicinal herbs, including Rheum officinale (8) and Polygonam cuspidatummedicine (9). It has been widely studied for its antibacterial, diuretic, immuno suppressive, anti-inflammatory and vaso relaxant effects. It has been reported that emodin induces apoptosis of several types of human cancer cells (10-13) by modulating various signaling pathways. However, the biological mechanisms by which emodin induces cytotoxicity remain largely unknown. Furthermore, the biological effects of emodin on breast cancer cells remain to be determined.In this study, the effects of emodin on the proliferation and apoptosis of breast cancer cells were assessed. In addition, the mechanism by which emodin mediates these biological effects was elucidated. We demonstrated that emodin inhibited the proliferation and induced apoptosis of Bcap-37 and ZR-75-30 breast cancer cells. These observations suggest that emodi...

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BackgroundAs a known regulator of apoptosis, survivin has positive relationship with lymphatic metastasis in breast cancer. This study aims to detect the difference in expression between survivin and vascular endothelial growth factor-C (VEGF-C) in treated breast cancer cells and tissues, and to analyze the correlation among survivin, VEGF-C and lymphatic metastasis.MethodsPlasmid with survivin and VEGF-C shRNA and lentivirus with survivin gene were constructed and transfected into breast cancer cell ZR-75-30. Then the expressions of the two genes were examined using western blot analysis and real-time PCR. The change of invasiveness of breast cancer cells was assessed using matrigel invasion assay. Using immunohistochemistry, the expression of survivin and VEGF-C were analyzed in 108 clinical breast cancer cases with breast cancer tissue and lymph node.ResultsSurvivin regulated the expression of VEGF-C at both protein and mRNA levels in breast cancer cells. Immunohistochemical analysis showed that the level of VEGF-C expression was significantly related with that of survivin in breast cancer tissues (p<0.05). VEGF-C was found to participate in the process of breast cancer cells invasion mediated by survivin. The co-expression of the two and the single expression of any one took significant difference in positive lymph node (p<0.05).ConclusionsSurvivin takes an important part in regulating the expression of VEGF-C. VEGF-C could influence the invasive ability mediated by survivin. The co-expression of survivin and VEGF-C is more statistically significant to assess lymphatic metastasis in breast cancer.Virtual slidesThe virtual slide(s) for this article can be found here: http://www.diagnosticpathology.diagnomx.eu/vs/9193530897100952

The development of drug resistance to chemotherapeutic agents has consistently presented a challenge in terms of the treatment of patients with triple-negative breast cancer (TNBC). In the present study, gemcitabine (dFdC)-resistant TNBC cells were established, and the effects of lentivirus-deoxyribonucleoside kinase (dNK) and a mutated form of dNK (lentivirus-dNKmut) on reversing the acquired drug resistance in dFdC-resistant TNBC cells were explored. Quantitative PCR and western blotting experiment results suggested that Drosophila melanogaster (Dm)-dNK was stably expressed in the lentivirus-infected MDA-MB-231 and MDA-MB-231R cells in the nucleus or cytosol, and autoradiography experiments revealed similar levels of enzymatic activity in the cells expressing dNK or dNKmut. In vitro cytotoxicity assay revealed that the IC 50 values of dFdC were decreased 30~50-fold in the dFdC-resistant MDA-MB-231 cells following lentiviral transfection with dNK or dNKmut, and this effect was associated with a significantly increased rate of apoptosis compared with the cells transfected with the negative control lentivirus. In conclusion, Dm-dNK in the nucleus or cytosol may be a potential candidate for reversing acquired dFdC resistance in TNBC cells, which may form the basis of novel strategies for the treatment of patients with drug-resistant TNBC.