ApoA-I mimetic administration, but not increased apoA-I-containing HDL, inhibits tumour growth in a mouse model of inherited breast cancer

作者：Cedo Lidia; Garcia Leon Annabel; Baila Rueda Lucia; Santos David; Grijalva Victor; Raquel Martinez Cignoni Melanie; Carbo Jose M; Metso Jari; Lopez Vilaro Laura; Zorzano Antonio; Valledor Annabel F; Cenarro Ana; Jauhiainen Matti; Lerma Enrique; Fogelman Alan M; Reddy Srinivasa T; Carles Escola Gil Joan; Blanco Vaca Francisco^*

来源：Scientific Reports, 2016, 6(1): 36387.

DOI：10.1038/srep36387

Low levels of high-density lipoprotein cholesterol (HDLc) have been associated with breast cancer risk, but several epidemiologic studies have reported contradictory results with regard to the relationship between apolipoprotein (apo) A-I and breast cancer. We aimed to determine the effects of human apoA-I overexpression and administration of specific apoA-I mimetic peptide (D-4F) on tumour progression by using mammary tumour virus-polyoma middle T-antigen transgenic (PyMT) mice as a model of inherited breast cancer. Expression of human apoA-I in the mice did not affect tumour onset and growth in PyMT transgenic mice, despite an increase in the HDLc level. In contrast, D-4F treatment significantly increased tumour latency and inhibited the development of tumours. The effects of D-4F on tumour development were independent of 27-hydroxycholesterol. However, D-4F treatment reduced the plasma oxidized low-density lipoprotein (oxLDL) levels in mice and prevented oxLDL-mediated proliferative response in human breast adenocarcinoma MCF-7 cells. In conclusion, our study shows that D-4F, but not apoA-I-containing HDL, hinders tumour growth in mice with inherited breast cancer in association with a higher protection against LDL oxidative modification.

• 出版日期2016-11-3