Breastfeeding is associated with a decreased risk of ovarian cancer. However, the mechanism underlying this apparent clinical benefit is unknown. Oxytocin (OXT), a hypothalamic nonapetide, plays a crucial role in many reproductive and behavioural functions. In recent year, OXT acts as a growth regulator in many kind of tumor tissues, through the activation of a specific G-coupled transmembrane receptor, the oxytocin receptor (OXTR). OXT has been proved to inhibit the proliferation, migration and invasion of ovarian cancer SKOV3 cells in vitro. But, the underlying mechanisms remain unknown. Here, we found OXT inhibited proliferation, and critically migration and invasion of human ovarian cancer cells SKOV3 and A2780. Strikingly, OXT inhibited ovarian cancer metastasis by repressing the expressions of MMP-2 and VEGF. Moreover, OXT inhibited vascular endothelial cell tube formation by reducing the VEGF production from ovarian cancer cells. Our findings may provide a possible explanation for breastfeeding-associated protective effects and suggest new therapeutic opportunities for ovarian cancer.
Stress is associated with an increased risk of lung metastasis in melanoma. However, the underlying mechanism is elusive. Oxytocin (OXT), a neurohormone produced by the hypothalamus, plays a vital role in laboring induction and lactation. Emerging evidence suggests that OXT also regulates human emotions, social cognition, social behaviors and stress-related disorders. Here, we reported that a significant up-regulation of oxytocin receptors (OXTRs) was observed in malignant melanoma. The activation of OXTRs dramatically promoted migration, invasion and angiogenesis but not the proliferation of melanoma cells in vitro and in vivo via β-arrestin 2-dependent ERK-VEGF/MMP-2 pathway. Next, chronic restraint stress significantly elevated the plasma level of OXT. Notably, 21 days chronic restraint stress facilitated lung metastasis of melanoma and reduced overall survival in mice, which were largely abrogated by knocking down either OXTR or β-arrestin 2. These findings provide evidence that chronic stress hormone-OXT promotes lung metastasis of melanoma via a β-arrestin 2-dependent mechanism and suggest that OXT, a novel pro-metastasis factor, is a potential therapeutic target for melanoma.
As a prevalent tumor among women, breast cancer is still an incurable disease due to drug resistance. In this study, we report microRNA‐221 to have a significant effect on breast cancer resistance to adriamycin. The microRNA‐221 is elevated in tumor tissue compared with nearby nontumor samples, as well as in breast cancer cell line with adriamycin resistance (MCF‐7/ADR) compared to its parental line (MCF‐7) and the normal breast epithelial cell line (MCF‐10A). Enforced level of microRNA‐221 promotes cancer resistance to adriamycin, which in turn sustains cell survival and exacerbates malignant formation. Reciprocally, the silence of microRNA‐221 in cancer cells augments the sensitivity to chemotherapy, thereby resulting in enhanced apoptosis of MCF‐7/ADR cells. Mechanistically, we identify PTEN as a direct target of microRNA‐221, which was conversely associated with a microRNA‐221 level in breast tumors. The knock‐down of PTEN partially reversed the stimulatory role of microRNA‐221 in the modulation of the Akt/mTOR signaling. Taken together, these findings suggest microRNA‐221 suppresses PTEN transcription and activates Akt/mTOR pathway, which in turn enhances breast cancer resistance to adriamycin and promotes cancer development. Our data thus illuminate the microRNA‐221/PTEN axis may act as a promising strategy for the treatment of chemotherapy‐resistant breast tumors.
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