Application of glucocorticoid receptor accelerator antcin A in inhibiting tumorigenesis and metastasis of breast cancer

Abstract

An application of a glucocorticoid receptor accelerator antcin A in inhibiting tumorigenesis and metastasis of breast cancer is disclosed, human breast cancer cells MCF-7 and MDA-MB-231 are treated byutilizing natural glucocorticoid analog antcin A, and then an miR-708 expression is significantly increased by activating a glucocorticoid receptor [alpha] (GR[alpha]). Induction of the miR-708 expression by a GR accelerant can effectively inhibit proliferation of human breast cancer cells, a cell cycle progression, and tumor stem cell expression and cancer cell metastasis. In addition, the GR accelerant or an miR-708 transfection treatment cell significantly inhibits an expression of IKK[belta], also inhibits the activity of NF-[kappa]B and the expression of its downstream target genes, andimproves amount of expression of involvement in cancer cell proliferation, the cell cycle progression, metastasis and cancer stem cells marker proteins p21<CIP1> and p27<KIP1>. Human breast cancer cell xenograft model tests find that treatment of animals with the GR accelerant can significantly inhibit tumor growth and tumor weight and volume. As a whole, a result of an experiment strongly speculates that the GR accelerant induces the miR-708 expression and inhibits NF-[kappa]B downstream signal transduction, and can be a novel treatment mode applied to breast cancer treatment.

Description

technical field [0001] The present invention relates to a glucocorticoid receptor promoter for inhibiting breast cancer tumorigenesis and metastasis, in particular to a synthetic or natural glucocorticoid receptor (GR) promoter that can induce microribose Nucleic acid-708 (microRNA-708, miR-708) expression, thereby inhibiting the occurrence and metastasis of breast cancer tumors, especially activating miR-708 through transcriptional activation of glucocorticoid receptor α (GRα), resulting in decreased proliferation of breast cancer cells and induction of cell cycle Stasis, mainly through the transcriptional repression of NF-κB and its target genes COX-2 and cMYC. Background technique [0002] Breast cancer is the most common malignancy and the leading cause of cancer-related death among women worldwide, with approximately 1.3 million new cases of breast cancer diagnosed each year and an estimated 500,000 deaths from breast cancer [1], according to the International Agency fo...

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Problems solved by technology

Furthermore, little is known about the regulation of miRNAs through GR promoter-mediated signaling pathways in breast cancer

Therefore, it generally cannot meet the needs of users in actual use.

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