| 陈挑调,柏建安,叶木杰,严丽军,潘佳玲,汤琪云.奥曲肽联合黄芩素抑制胰腺神经内分泌肿瘤细胞增殖和迁移[J].,2022,(12):2201-2207 |
| 奥曲肽联合黄芩素抑制胰腺神经内分泌肿瘤细胞增殖和迁移 |
| Octreotide Combined with Baicalein Inhibits the Proliferation and Migration of Pancreatic Neuroendocrine Neoplasms |
| 投稿时间：2022-01-29 修订日期：2022-02-27 |
| DOI：10.13241/j.cnki.pmb.2022.12.001 |
| 中文关键词: 胰腺神经内分泌肿瘤 奥曲肽 黄芩素 增殖 迁移 |
| 英文关键词: Pancreatic neuroendocrine neoplasms Octreotide Baicalein Proliferation Migration |
| 基金项目:国家自然科学基金青年基金项目（82003256）；江苏省第五期"333"工程项目( BRA2017535) |
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| 中文摘要: |
| 摘要 目的：探讨奥曲肽（Octreotide，Oct）联合黄芩素（Baicalein，BE）对胰腺神经内分泌肿瘤（Pancreatic neuroendocrine neoplasms, pNENs）的影响。方法：用不同浓度的奥曲肽和黄芩素处理pNENs来源的QGP-1细胞，CCK8法检测细胞的存活率，以其半抑制浓度（IC50）的比值作为浓度梯度进行联合用药，并用Compusyn软件进行联合指数（CI）分析，取细胞毒性效应适中且CI值较低的浓度（奥曲肽150 μmol/L，黄芩素20 μmol/L）进行表型实验。将QGP-1细胞分为四组：对照组、奥曲肽组、黄芩素组、奥曲肽和黄芩素联用组。通过克隆形成实验、EdU增殖检测、划痕实验、细胞凋亡和周期检测评价四组细胞的增殖、迁移能力以及凋亡和细胞周期的情况。结果：药物处理24 h后，奥曲肽和黄芩素均能够呈浓度依赖性抑制QGP-1细胞增殖（P<0.05），奥曲肽的IC50为329.90 μmol/L，黄芩素的IC50为42.86 μmol/L，两者IC50的比值约为7.5:1，联用组细胞活性明显低于单药组（P<0.05），且CI值随着药物浓度的增加而降低。克隆形成实验和EdU增殖检测结果表明，奥曲肽和黄芩素均可抑制QGP-1细胞增殖（P<0.05），且联用组的克隆形成率和EdU阳性细胞百分比均低于单药组（P<0.05）。划痕实验结果表明，奥曲肽和黄芩素均可降低QGP-1细胞的迁移率（P<0.05），且联用组的迁移率低于单药组（P<0.05）。细胞凋亡和周期检测结果表明，黄芩素可促进QGP-1细胞的凋亡（P<0.05），并使QGP-1细胞阻滞于G0/G1期（P<0.05），而奥曲肽对QGP-1细胞的凋亡和细胞周期无明显影响（P>0.05），两药联用对其凋亡和周期无协同作用。结论：奥曲肽和黄芩素联合用药可协同抑制QGP-1细胞增殖和迁移，对细胞凋亡和周期无明显协同作用。 |
| 英文摘要: |
| ABSTRACT Objective: To investigate the effect of octreotide combined with baicalein inhibits the proliferation and migration of pancreatic neuroendocrine neoplasms (pNENs). Methods: QGP-1 cells derived from pNENs were treated with different concentrations of octreotide and baicalein, and cell viability was detected by CCK8. The ratio of semi-inhibitory concentration (IC50) was used as the concentration gradient for combination drugs. The combination index (CI) analysis was analyzed by Compusyn software, and the concentrations with moderate cytotoxicity and low CI value (octreotide 150 μmol/L, baicalein 20 μmol/L) were selected for phenotypic experiments. QGP-1 cells were divided into four groups: control group, octreotide group, baicalein group and combined group. The proliferation, migration, apoptosis and cell cycle of the four groups were evaluated by colony formation assay, EdU proliferation assay, wound healing assay, apoptosis and cell cycle assay. Results: After 24 hours of treatment, octreotide and baicalein could inhibit the proliferation of QGP-1 cells in a concentration-dependent manner (P<0.05). The IC50 of octreotide was 329.90 μmol/L, the IC50 of baicalein was 42.86 μmol/L, and the ratio of IC50 was 7.5:1. The cell viability in the combined group was significantly lower than that in the single drug group (P<0.05), and the CI value decreased with the increase of drug concentration. The results of colony formation assay and EdU proliferation assay showed that both octreotide and baicalein could inhibit the proliferation of QGP-1 cells (P<0.05), and the colony formation rate and the percentage of EdU positive cells in the combination group were lower than those in the single drug group (P<0.05). The results of wound healing assay showed that both octreotide and baicalein could reduce the migration rate of QGP-1 cells (P<0.05), and the migration rate in the combination group was lower than that in the single drug group (P<0.05). The results of apoptosis and cell cycle assay showed that baicalein could promote the apoptosis of QGP-1 cells (P<0.05) and block QGP-1 cells in G0/G1 phase (P<0.05), while octreotide had no significant effect on apoptosis and cell cycle of QGP-1 cells (P>0.05), and the combination of octreotide and baicalein had no synergistic effect on apoptosis and cell cycle. Conclusion: Octreotide and baicalein can synergistically inhibit the proliferation and migration of QGP-1 cells, but have no obvious synergistic effect on apoptosis and cell cycle. |
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