Abstract
The α9-containing nicotinic acetylcholine receptor (nAChR) is increasingly emerging as a new tumor target owing to its high expression specificity in breast cancer. αO-Conotoxin GeXIVA is a potent antagonist of α9α10 nAChR. Nevertheless, the anti-tumor effect of GeXIVA on breast cancer cells remains unclear. Cell Counting Kit-8 assay was used to study the cell viability of breast cancer MDA-MD-157 cells and human normal breast epithelial cells, which were exposed to different doses of GeXIVA. Flow cytometry was adopted to detect the cell cycle arrest and apoptosis of GeXIVA in breast cancer cells. Migration ability was analyzed by wound healing assay. Western blot (WB), quantitative real-time PCR (QRT-PCR) and flow cytometry were used to determine expression of α9-nAChR. Stable MDA-MB-157 breast cancer cell line, with the α9-nAChR subunit knocked out (KO), was established using the CRISPR/Cas9 technique. GeXIVA was able to significantly inhibit the proliferation and promote apoptosis of breast cancer MDA-MB-157 cells. Furthermore, the proliferation of breast cancer MDA-MB-157 cells was inhibited by GeXIVA, which caused cell cycle arrest through downregulating α9-nAChR. GeXIVA could suppress MDA-MB-157 cell migration as well. This demonstrates that GeXIVA induced a downregulation of α9-nAChR expression, and the growth of MDA-MB-157 α9-nAChR KO cell line was inhibited as well, due to α9-nAChR deletion. GeXIVA inhibits the growth of breast cancer cell MDA-MB-157 cells in vitro and may occur in a mechanism abolishing α9-nAChR.
Highlights
Cancer is the second leading cause of death worldwide, and it was estimated to account for9.6 million deaths in 2018 [1]
GeXIVA induced a downregulation of α9-nicotinic acetylcholine receptor (nAChR) expression, and the growth of MDA-MB-157
The results showed that the content of GeXIVA decreased while the serum concentration increased, and as time went on remaining amounts of GeXIVA were ~93%, ~73%, ~66% and ~54% respectively
Summary
Cancer is the second leading cause of death worldwide, and it was estimated to account for9.6 million deaths in 2018 [1]. Cancer is the second leading cause of death worldwide, and it was estimated to account for. Breast cancer is the second most common carcinoma in the world after lung cancer, and is the highest-incidence cancer among women. Breast cancer remains the leading cause of cancer incidence and mortality, with 2.1 million newly diagnosed cases and 630 thousand deaths in 2018 [1,2]. Genetic and reproductive risk factors play important roles in susceptibility to breast cancer [3]. Conventional therapeutic strategies usually provide limited specificity, resulting in severe side effects and toxicity to normal organisms. Targeted cancer therapy could improve the therapeutic potential of anti-tumor agents and reduce adverse side effects [4]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
