Suppression of αvβ6 downregulates P-glycoprotein and sensitizes multidrug-resistant breast cancer cells to anticancer drugs.

Suppression of αvβ6 downregulates P-glycoprotein and sensitizes multidrug-resistant breast cancer cells to anticancer drugs. Neoplasma. 2020 Feb 09;: Authors: Zhang YH, Gao ZF, Dong GH, Li X, Wu Y, Li G, Wang AL, Li HL, Yin DL Abstract Multidrug resistance (MDR) in breast cancer treatment is the major cause leading to the failure of chemotherapy. P-glycoprotein (P-gp), the product of the human MDR1 gene, plays a key role in resistance to chemotherapy and confers a cross-resistance to many structurally unrelated anticancer drugs. We previously have reported that integrin αvβ6 plays a critical role in breast cancer invasion and metastasis. However, whether and how αvβ6 is associated with P-gp and regulated by potential genetic mechanisms in breast cancer still remains unclear. In the present study, we further investigated the reversal effect and underlying mechanisms of MDR in breast cancer. Two small interfering RNA constructs (pSUPER-β6shRNAs) targeting two different regions of the β6 gene have been designed to inhibit αvβ6 expression by transfecting them into adriamycin-resistant MCF-7/ADR cell lines. Suppression of αvβ6 dramatically downregulated the levels of MDR1 gene mRNA and P-gp. In particular, β6shRNA-mediated silencing of αvβ6 gene increased significantly the cellular accumulation of Rhodamine 123 and markedly decreased drug efflux ability, suggesting that β6shRNAs indeed inhibit P-gp mediated drug efflux and...
Source: Neoplasma - Category: Cancer & Oncology Authors: Tags: Neoplasma Source Type: research