Abstract
Tamoxifen resistance remains the major obstacle to the estrogen receptor positive breast cancer endocrine therapy. Placenta-specific 8 (PLAC8) has been implicated in epithelial-mesenchymal transition and tumorigenesis. However, the molecular mechanisms underlying PLAC8 function in the context of tamoxifen resistance are unclear. Curcumin has attracted considerable attention in the last decades. It is isolated from Curcuma longa and has beneficial effects in cancer therapy. We studied this property by using MCF-7 and tamoxifen-resistant breast cancer cells (MCF-7/TAM) cell lines. PLAC8 can regulate MCF-7/TAM cell drug sensitivity through the MAPK/ERK pathway and shows the potential effects of curcumin or as a possible druggable target against tamoxifen failure.
Highlights
Breast cancer (BC) is the most common malignant tumor and the second leading cause of cancer-related death in women [1, 2]
MTT assay results showed that Placentaspecific 8 (PLAC8) could induce cell proliferation both in MCF-7 and MCF-7/TAM (Fig. 2c and d)
We observed that silencing PLAC8 in MCF-7/TAM would significantly increase tamoxifen sensitivity and tamoxifen futher inhibited Si-PLAC8 group cells compared with SiNC group cells (Fig. 3a).These results determined that PLAC8 could promote cell proliferation, and induce tamoxifen resistance
Summary
Breast cancer (BC) is the most common malignant tumor and the second leading cause of cancer-related death in women [1, 2]. PLAC8 was found to be highly expressed in the mouse placenta [7]. Accumulating evidence have shown that PLAC8 is involved in the participation of cancer processes, including in the hepatocellular carcinoma, nasopharyngeal carcinoma and lung cancer [8,9,10]. PLAC8 has a pivotal oncogenic or tumor suppressor role in cancer progression. We have confirmed that PLAC8 can suppress breast cancer apoptosis by activating the PI3k/AKT/NF-κB pathway [11]. Whether PLAC8 is involved in tamoxifen resistance in breast cancer is still unclear. A major component of the rhizome of Curcuma longa, interacts with various proteins and regulates their expression and activity, including PI3K/Akt, NF-kB, and c-Myc [12,13,14]. Curcumin influences the proliferation of breast cancer cells and other types of cancer cells, such as gastric cancer cell, esophageal squamous cell
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