Journal
TRANSLATIONAL ONCOLOGY
Volume 14, Issue 10, Pages -Publisher
ELSEVIER SCIENCE INC
DOI: 10.1016/j.tranon.2021.101181
Keywords
ABCB1; Breast cancer; Drug resistance; Cyclooxygenase; Histone deacetylase inhibitor
Categories
Funding
- NIH [U54CA209978]
- National Cancer Institute of the National Institutes of Health [P30CA033572]
Ask authors/readers for more resources
The overexpression of ABCB1 in cancer cells leads to drug resistance, but combination therapy with specific drugs and chemotherapy can enhance treatment efficacy; further studies are needed to explore the clinical potential of tepoxalin in restoring chemosensitivity in patients with drug-resistant breast cancer due to ABCB1 overexpression.
Effective cancer chemotherapy treatment requires both therapy delivery and retention by malignant cells. Cancer cell overexpression of the multidrug transmembrane transporter gene ABCB1 (MDR1, multi-drug resistance protein 1) thwarts therapy retention, leading to a drug-resistant phenotype. We explored the phenotypic impact of ABCB1 overexpression in normal human mammary epithelial cells (HMECs) via acute adenoviral delivery and in breast cancer cell lines with stable integration of inducible ABCB1 expression. One hundred sixty-two genes were differentially expressed between ABCB1-expressing and GFP-expressing HMECs, including the gene encoding the cyclooxygenase-2 protein, PTGS2. Several breast cancer cell lines with inducible ABCB1 expression demonstrated sensitivity to the 5-lipoxygenase, cyclooxygenase-1/2 inhibitor tepoxalin in two-dimensional drug response assays, and combination treatment of tepoxalin either with chemotherapies or with histone deacetylase (HDAC) inhibitors improved therapeutic efficacy in these lines. Moreover, selection for the ABCB1-expressing cell population was reduced in three-dimensional co-cultures of ABCB1-expressing and GFP-expressing cells when chemotherapy was given in combination with tepoxalin. Further study is warranted to ascertain the clinical potential of tepoxalin, an FDA-approved therapeutic for use in domesticated mammals, to restore chemosensitivity and improve drug response in patients with ABCB1-overexpressing drug-resistant breast cancers.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available