αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors
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...
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MDPI AG
2020-04-01
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| Series: | Marine Drugs |
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| Online Access: | https://www.mdpi.com/1660-3397/18/4/195 |
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| author | Zhihua Sun Jiaolin Bao Manqi Zhangsun Shuai Dong Dongting Zhangsun Sulan Luo |
| author_facet | Zhihua Sun Jiaolin Bao Manqi Zhangsun Shuai Dong Dongting Zhangsun Sulan Luo |
| author_sort | Zhihua Sun |
| collection | DOAJ |
| description | 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 <i>in vitro</i> and may occur in a mechanism abolishing α9-nAChR. |
| first_indexed | 2024-03-10T20:37:33Z |
| format | Article |
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| issn | 1660-3397 |
| language | English |
| last_indexed | 2024-03-10T20:37:33Z |
| publishDate | 2020-04-01 |
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| record_format | Article |
| series | Marine Drugs |
| spelling | doaj.art-2ede29ec52494d108e0cb59080a1d1aa2023-11-19T20:54:55ZengMDPI AGMarine Drugs1660-33972020-04-0118419510.3390/md18040195αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine ReceptorsZhihua Sun0Jiaolin Bao1Manqi Zhangsun2Shuai Dong3Dongting Zhangsun4Sulan Luo5Key Laboratory of Tropical Biological Resources of Ministry of Education, Key Laboratory for Marine Drugs of Haikou, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, Key Laboratory for Marine Drugs of Haikou, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, Key Laboratory for Marine Drugs of Haikou, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaKey Laboratory of Tropical Biological Resources of Ministry of Education, Key Laboratory for Marine Drugs of Haikou, School of Life and Pharmaceutical Sciences, Hainan University, Haikou 570228, ChinaMedical School, Guangxi University, Nanning 530004, ChinaMedical School, Guangxi University, Nanning 530004, ChinaThe 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 <i>in vitro</i> and may occur in a mechanism abolishing α9-nAChR.https://www.mdpi.com/1660-3397/18/4/195α9-nicotinic acetylcholine receptors (nAChRs)breast cancer cellsαO-conotoxin GeXIVAapoptosisanti-proliferationtargeted therapy |
| spellingShingle | Zhihua Sun Jiaolin Bao Manqi Zhangsun Shuai Dong Dongting Zhangsun Sulan Luo αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors Marine Drugs α9-nicotinic acetylcholine receptors (nAChRs) breast cancer cells αO-conotoxin GeXIVA apoptosis anti-proliferation targeted therapy |
| title | αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors |
| title_full | αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors |
| title_fullStr | αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors |
| title_full_unstemmed | αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors |
| title_short | αO-Conotoxin GeXIVA Inhibits the Growth of Breast Cancer Cells via Interaction with α9 Nicotine Acetylcholine Receptors |
| title_sort | αo conotoxin gexiva inhibits the growth of breast cancer cells via interaction with α9 nicotine acetylcholine receptors |
| topic | α9-nicotinic acetylcholine receptors (nAChRs) breast cancer cells αO-conotoxin GeXIVA apoptosis anti-proliferation targeted therapy |
| url | https://www.mdpi.com/1660-3397/18/4/195 |
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