Abstract
Triple negative breast cancer (TNBC) has significantly threatened human health. Many aspects of TNBC are closely related to Wnt/β-catenin pathway, and cell apoptosis induced by endoplasmic reticulum stress (ER stress) in TNBC may act as a potential target of non-chemotherapy treatment. However, how ER stress interacts with this pathway in TNBC has not yet been understood. Here, the tunicamycin and LiCl have been applied to MDA-MB-231. The related proteins' expression was measured by western blotting. Moreover, acridine orange/ethidium bromide (AO/EB) staining was applied to test the apoptosis degree of the cells, and cell viability was tested by MTT experiment. Then, we found the ER stress and apoptosis degree of MDA-MB-231 were induced after treatment with tunicamycin. Besides, tunicamycin dose dependently inhibited both Wnt/β-catenin pathway and cells viability. Licl, an activator of Wnt/β-catenin signaling pathway, could significantly inhibit cell apoptosis. In conclusion, our study found that the activation of ER stress could promote the MDA-MB-231 apoptosis by repressing Wnt/β-catenin pathway, which provides some promising prospects and basic mechanism to the further research.
Highlights
All over the world, breast cancer has become the most severe cancer in women [1, 2]
To detect the influence of tunicamycin for MDA-MB-231, the various concentration of drug was used to treat cells to determine their optimal concentration. e results showed that the estrogen receptors (ERs) stress key molecules GRP78 and CHOP increased as the dose of tunicamycin increased from nil to 2 μmol/L (Figure 1(a))
To further evaluate the results of this experiment, the viability of cell was measured by MTT. e cell viability increased as the drug dose increased and reached a maximum at a dose of 1 μmol/L of tunicamycin (Figure 1(d)). erefore, the function of tunicamycin on cells and its suppressive effect in Wnt/β-catenin pathway is obvious when the concentration is at 1 μmol/L; in further experiments, this concentration was selected
Summary
Breast cancer has become the most severe cancer in women [1, 2]. In addition, triple-negative breast cancer (TNBC), with the worst prognosis as it lacks estrogen receptors (ERs), human epidermal growth factor receptor 2 (HER2), and progesterone receptors (PRs), has the highest mortality compared to the other types of breast cancer [3, 4]. A lot of research has investigated the relationship between breast cancer and Wnt/β-catenin signaling pathway [5, 6], which states that the initiation of Wnt/β-catenin pathway triggers the poor prognosis for TNBC [7]. Endoplasmic reticulum (ER) stress has a certain toxic effect on cells, and it can be activated by a variety of stimuli, such as large amount of unfolded protein accumulation in cells, disorder of redox response, and calcium regulation disorder [10, 11]. Zhong et al investigated the mechanism that promoting ER stress could cause the autophagy, apoptosis, and chemosensitivity of breast cancer through the PI3K/AKT/mTOR signaling pathway [13]. E relationship between ER stress, unfolded protein response, and apoptosis provides novel molecular targets for breast cancer treatment Zhong et al investigated the mechanism that promoting ER stress could cause the autophagy, apoptosis, and chemosensitivity of breast cancer through the PI3K/AKT/mTOR signaling pathway [13]. e relationship between ER stress, unfolded protein response, and apoptosis provides novel molecular targets for breast cancer treatment
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