Establishment of paclitaxel-resistant breast cancer cell line and nude mice models, and underlying multidrug resistance mechanisms in vitro and in vivo.

Content Provider	Semantic Scholar
Author	Chen, Si-Ying Hu, Sa-Sa Dong, Qian Cai, Jianyong Zhang, Wei-Peng Sun, Jin-Yao Wang, Tao-Tao Xie, Jiao He, Hai-Rong Xing, Jian-Feng Dong, Yalin
Copyright Year	2013
Abstract	BACKGROUND Breast cancer is a common malignant tumor which affects health of women and multidrug resistance (MDR) is one of the main factors leading to failure of chemotherapy. This study was conducted to establish paclitaxel-resistant breast cancer cell line and nude mice models to explore underlying mechanisms of MDR. METHODS The breast cancer drug-sensitive cell line MCF-7 (MCF-7/S) was exposed in stepwise escalating paclitaxel (TAX) to induce a resistant cell line MCF-7/TAX. Cell sensitivity to drugs and growth curves were measured by MTT assay. Changes of cell morphology and ultrastructure were examined by optical and electron microscopy. The cell cycle distribution was determined by flow cytometry. Furthermore, expression of proteins related to breast cancer occurrence and MDR was tested by immunocytochemistry. In Vivo, nude mice were injected with MCF-7/S and MCF-7/TAX cells and weights and tumor sizes were observed after paclitaxel treatment. In addition, proteins involved breast cancer and MDR were detected by immunohistochemistry. RESULTS Compared to MCF-7/S, MCF-7/TAX cells had a higher resistance to paclitaxel, cross-resistance and prolonged doubling time. Moreover, MCF-7/TAX showed obvious alterations of ultrastructure. Estrogen receptor (ER) expression was low in drug resistant cells and tumors while expression of human epidermal growth factor receptor 2 (HER2) and Ki-67 was up-regulated. P-glycoprotein (P-gp), lung resistance-related protein (LRP) and glutathione-S-transferase-π (GST-π) involved in the MDR phenotype of resistant cells and tumors were all overexpressed. CONCLUSION The underlying MDR mechanism of breast cancer may involve increased expression of P-gp, LRP and GST-π.
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Alternate Webpage(s)	http://ocean.kisti.re.kr/downfile/volume/apocp/POCPA9/2013/v14n10/POCPA9_2013_v14n10_6135.pdf
PubMed reference number	24289639v1
Volume Number	14
Issue Number	10
Journal	Asian Pacific journal of cancer prevention : APJCP
Language	English
Access Restriction	Open
Subject Keyword	Antineoplastic Agents Breast Cancer Cell Breast Carcinoma Cell Cycle Cellular Morphology Estrogens Flow Cytometry Glutathione Growth Factor Receptors MVP gene Malignant neoplasm of breast Mammary Neoplasms Multi-Drug Resistance P-Glycoproteins Paclitaxel Structure of parenchyma of lung Weight monooxyethylene trimethylolpropane tristearate
Content Type	Text
Resource Type	Article