| 侯海涛,尚翠霞,邓景元,等.抑制Yes-相关蛋白表达促进芬太尼诱导乳腺癌细胞凋亡的研究[J].中国临床保健杂志,2021,24(4):512-517. |
| 抑制Yes-相关蛋白表达促进芬太尼诱导乳腺癌细胞凋亡的研究 |
| The inhibition of the expression of Yes-related proteins promotes fentanyl-induced apoptosis of breast cancer cells |
| 投稿时间：2021-04-13 |
| DOI：10.3969/J.issn.1672-6790.2021.04.017 |
| 中文关键词: 乳腺肿瘤 细胞增殖 细胞凋亡 芬太尼 信号传导 |
| 英文关键词: Breast neoplasms Cell proliferation Apoptosis Fentanyl Signal transduction |
| 基金项目: |
| 作者 | 单位 | E-mail | | 侯海涛 | 西安交通大学第一附属医院,康复医学科,西安 710061 | hht258@126.com | | 尚翠霞 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 邓景元 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 崔延超 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 赵昭 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 陆鹏 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 沈剑南 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 马姣 | 西安交通大学第一附属医院,康复医学科,西安 710061 | | | 姚力 | 西安交通大学第一附属医院,康复医学科,胸外科,西安 710061 | |
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| 中文摘要: |
| 目的 探讨芬太尼调控Yes-相关蛋白(YAP)在乳腺癌细胞增殖凋亡中的作用及机制。方法 细胞增殖试验(MTT)检测乳腺癌细胞MCF-7增殖,流式细胞术检测细胞凋亡,Western Blots检测相关蛋白表达,荷瘤小鼠体内验证芬太尼及YAP对乳腺癌生长的作用,Student t检验用于比较两组间的差异。结果 芬太尼(2 μg/L)可抑制乳腺癌细胞的增殖并促进其凋亡,当敲除YAP蛋白表达后,该作用显著增强。芬太尼促进乳腺癌细胞中YAP蛋白的去磷酸化但不影响其表达,去磷酸化后的YAP高表达于细胞核中,并可促进YAP下游蛋白Survivin及Bcl2的表达。抑制μ阿片受体(MOR)、Gi的活性可逆转芬太尼诱导的YAP去磷酸化。芬太尼显著抑制YAP低表达MCF-7细胞荷瘤小鼠肿瘤生长,而对正常MCF-7细胞荷瘤小鼠肿瘤生长影响不显著。结论 芬太尼可通过激活乳腺癌细胞中YAP信号通路；抑制乳腺癌细胞YAP表达,可促进芬太尼诱导的乳腺癌细胞凋亡。 |
| 英文摘要: |
| Objective To explore the role and mechanism of fentanyl in regulating Yes-related protein (YAP) in the proliferation and apoptosis of breast cancer cells.Methods MTT was used to detect the proliferation of MCF-7 cells,and cell apoptosis was detected by flow cytometry,protein expression was detected by Western Blots,and the effect of fentanyl and YAP on breast cancer growth was verified in tumor-bearing mice.Student′s T-test was used to compare the differences between the two groups.Results Fentanyl (2 μg/L) inhibited the proliferation and promoted the apoptosis of breast cancer cells,and the effect was significantly enhanced when the expression of YAP protein was knocked out.Fentanyl promoted the dephosphorylation of YAP in breast cancer cells,but did not affect its expression.The dephosphorylated YAP was highly expressed in the nucleus,and it also promoted the expression of Survivin and Bcl2 proteins downstream of YAP.Inhibited the activity of μopioid receptor (MOR) and GI could reversed fentanyl-induced dephosphorylation of YAP.Moreover,fentanyl significantly inhibited the tumor growth of MCF-7 cell bearing mice with low YAP expression,but had no significant effect on the tumor growth of normal MCF-7 cell bearing mice.Conclusion Fentanyl can promote the apoptosis of breast cancer cells by activating the YAP signaling pathway and inhibiting the expression of YAP in breast cancer cells. |
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