Key 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, Hainan, China.
Mar Drugs. 2020 Jan 17;18(1):61. doi: 10.3390/md18010061.
Nicotinic acetylcholine receptors (nAChRs) are membrane receptors and play a major role in tumorigenesis and cancer progression. Here, we have investigated the differential expression of nAChR subunits in human breast cancer cell lines and breast epithelial cell lines at mRNA and protein levels and the effects of the αO-conotoxin GeXIVA, antagonist of α9α10 nAChR, on human breast cancer cells. Reverse transcription polymerase chain reaction (PCR) demonstrated that all nAChR subunits, except α6, were expressed in the 20 tested cell lines. Real time quantitative PCR (QRT-PCR) suggested that the mRNA of α5, α7, α9 and β4 nAChR subunits were overexpressed in all the breast cancer cell lines compared with the normal epithelial cell line HS578BST. α9 nAChR was highly expressed in almost all the breast cancer cell lines in comparison to normal cells. The different expression is prominent ( < 0.001) as determined by flow cytometry and Western blotting, except for MDA-MB-453 and HCC1395 cell lines. αO-conotoxin GeXIVA that targeted α9α10 nAChR were able to significantly inhibit breast cancer cell proliferation in vitro and merits further investigation as potential agents for targeted therapy.
烟碱型乙酰胆碱受体（nAChRs）是一种膜受体，在肿瘤发生和癌症进展中起主要作用。在这里，我们研究了 nAChR 亚基在人乳腺癌细胞系和乳腺上皮细胞系中的 mRNA 和蛋白水平的差异表达，以及αO-芋螺毒素 GeXIVA（α9α10 nAChR 的拮抗剂）对人乳腺癌细胞的影响。逆转录聚合酶链反应（PCR）表明，在 20 种检测的细胞系中，除了α6 之外，所有 nAChR 亚基均有表达。实时定量 PCR（QRT-PCR）表明，与正常上皮细胞系 HS578BST 相比，所有乳腺癌细胞系中α5、α7、α9 和β4 nAChR 亚基的 mRNA 表达均过度表达。与正常细胞相比，α9 nAChR 在几乎所有乳腺癌细胞系中均高度表达。通过流式细胞术和 Western blot 分析，除 MDA-MB-453 和 HCC1395 细胞系外，不同表达水平差异显著（<0.001）。靶向α9α10 nAChR 的αO-芋螺毒素 GeXIVA 能够显著抑制体外乳腺癌细胞增殖，值得进一步研究作为靶向治疗的潜在药物。
