Abstract
Opioids are a potential adjuvant treatment for certain cancers; while they are primarily used to relieve chronic pain, these drugs may also affect cancer progression and recurrence. Dezocine is one opioid commonly used in China, but its effects on cancer cells are unknown. Here, we demonstrated the inhibitory effect of dezocine on triple-negative breast cancer (TNBC) cells, and determined the underlying molecular mechanism. We found that dezocine suppressed cell proliferation, migration and invasion, and induced apoptosis in TNBC cells. Xenograft models demonstrated the inhibitory effects of dezocine treatment on TNBC tumor growth in vivo. The anticancer effects of dezocine were independent of opioid receptors, which are not highly expressed by normal breast or breast cancer tissues. A pull-down assay and LC-MS/MS analysis indicated that dezocine directly targets NAMPT: computer modeling verified that the free energy of dezocine kinetically bound into the pocket of NAMPT was −17.4 kcal/mol. Consequently, dezocine treatment inhibited NAMPT enzyme activity, resulting in cellular NAD abolishment. We confirmed the dezocine-induced inhibition of cell proliferation by both NAMPT knockdown and upon treatment with the inhibitor FK866. Our results suggest that both dezocine and NAMPT might represent novel therapeutic targets for TNBC.
Highlights
Breast cancer is the most common malignancy suffered by women, accounting for 30% of all diagnosed cases (Siegel et al, 2019)
We initially tested the effect of dezocine treatment on cell viability in a range of cell lines, which included triple negative breast cancer (TNBC), estrogen receptor (ER)-positive breast cancer and mammary epithelial cell lines
Colony formation assays further confirmed the dose-dependent, dezocine-induced inhibition of MDA-MB-231 and BT549 TNBC cell proliferation, with fewer cells visible on the plates as the dose increased from 10 μg/ml to 20 μg/ml (Figures 1C,D)
Summary
Breast cancer is the most common malignancy suffered by women, accounting for 30% of all diagnosed cases (Siegel et al, 2019). One example is triple negative breast cancer (TNBC), which accounts for 15% of all diagnosed breast carcinomas and is characterized by a lack of estrogen receptor (ER), progesterone receptor (PR), and human epidermal growth factor receptor 2 (HER2) expression (Waks and Winer, 2019). This means that traditional treatments that target these. The heterogenous nature of the disease means that even these aggressive, combination treatment regimens are often ineffective, and novel treatment approaches are urgently required to improve prognosis for patients with TNBC
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