| 罗 雨,钱 易,黄 海.硼替佐米联合5-氮杂胞苷对甲状腺未分化癌细胞增殖、侵袭能力及miR-124、miR-7、IL-11表达的影响[J].肿瘤学杂志,2019,25(6):498-502. |
| 硼替佐米联合5-氮杂胞苷对甲状腺未分化癌细胞增殖、侵袭能力及miR-124、miR-7、IL-11表达的影响 |
| Effects of Bortezomib Combined with 5-azacytidine on Proliferation，Invasion and miR-124，miR-7 and IL-11 Expression in Thyroid Undifferentiated Cancer Cells |
| 投稿时间：2019-02-14 |
| DOI：10.11735/j.issn.1671-170X.2019.06.B003 |
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| 中文关键词: 甲状腺肿瘤 硼替佐米 5-氮杂胞苷 miR-124 miR-7 白细胞介素-11 |
| 英文关键词:thyroid cancer bortezomib 5-azacytidine miR-124 miR-7 interleukin-11 |
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| 中文摘要: |
| 摘 要：［目的］ 探讨硼替佐米联合5-氮杂胞苷对甲状腺未分化癌细胞增殖、侵袭能力及miR-124、miR-7、白细胞介素-11（IL-11）水平的影响。［方法］ 计算硼替佐米和5-氮杂胞苷的IC50值，检测硼替佐米（Bor组）和5-氮杂胞苷（5-Aza组）单独和联合使用（5-Aza+Bor组）对甲状腺未分化癌细胞ARO细胞活力、凋亡率、迁移和侵袭能力的影响，并检测各组miR-124、miR-7、IL-11水平。采用CCK-8和流式细胞术检测细胞凋亡情况。采用细胞划痕实验和Transwell法分析细胞迁移和侵袭情况，采用qPCR法检测miRNA和mRNA水平，WB法检测蛋白的相对表达水平。［结果］ 硼替佐米和5-氮杂胞苷的IC50值分别为110ng/ml和5.5μmol/L。培养24h后Bor组和5-Aza组的细胞活力显著低于Control组，而细胞凋亡率显著高于Control组，且5-Aza+Bor组细胞活力（0.44±0.08）显著低于Bor组和5-Aza组（F=5.142，4.456；P均<0.001），而凋亡率（19.78%±1.67%）显著高于Bor组和5-Aza组（F=6.664，6.582；P均<0.001）。作用24h后，5-Aza+Bor组的迁移（31.78%±2.28%）（F=10.455，9.832；P均<0.001）和侵袭率（28.74%±2.15%）（F=11.135，10.739；P均<0.001）均显著低于Bor组和5-Aza组。5-Aza+ Bor组的miR-124、miR-7水平显著高于Bor组和5-Aza组（P<0.01），Bor组和5-Aza组IL-11显著低Control组（P<0.01），5-Aza+ Bor组的IL-11显著低于Bor组和5-Aza组（P<0.01）。［结论］ 硼替佐米与5-氮杂胞苷联合使用与单独使用相比，可进一步的抑制甲状腺未分化癌细胞增殖、迁移和侵袭，并促进其凋亡，可能与其可上调miR-124、miR-7水平和抑制IL-11的表达有关。 |
| 英文摘要: |
| Abstract：［Objective］ To investigate the effects of bortezomib combined with 5-azacytidine on proliferation，invasion and miR-124，miR-7 and interleukin-11(IL-11) levels in thyroid undifferentiated cancer cells. Methods］ The IC50 values of bortezomib and 5-azacytidine was calculated，respectively. The effectts of bortezomib (Bor group) and 5-azacytidine (5-Aza group) alone or in combination(5-Aza+Bor group) on ARO cell viability，apoptosis rate，migration and invasion were detected.The levels of miR-124，miR-7，and IL-11 in each group were examined. Apoptosis in cell viability were detected by CCK-8 and flow cytometry. Migration and invasion were detected by cell scratch assays and Transwell assay，miRNA and mRNA levels was detected by qPCR，and relative expression levels of proteins was detected by WB. ［Results］ After 24 h of culture，the cell viability of the Bor group and the 5-Aza group was significantly lower than that of the control group，and the apoptosis rate was significantly higher than that of the control group，and the 5-Aza+Bor cell viability (0.44±0.08) was significantly lower than that of the Bor group and 5-Aza group(F=5.142，4.456；all P<0.001). The apoptotic rate(19.78%±1.67%) was significantly higher than that in the Bor group and the 5-Aza group (F=6.664；6.582；all P<0.001). After 24 h，the migration(31.78%±2.28%) and the invasive rate(28.74%±2.15%) in the 5-Aza+Bor group were significantly lower than those in the Bor group and the 5-Aza group(F=10.455，9.832，all P<0.001；F=11.135，10.739，all P<0.001). The levels of miR-124 and miR-7 in 5-Aza+ Bor group were significantly higher than those in Bor group and 5-Aza group(P<0.01). The IL-11 of the Bor group and the 5-Aza group were significantly lower in the control group(P<0.01)，and the IL-11 in the 5-Aza+ Bor group was significantly lower than that in the Bor group and the 5-Aza group(P<0.01). ［Conclusion］The combination of bortezomib and 5-azacytidine can further inhibit the proliferation，migration and invasion of thyroid undifferentiated cancer cells and promote their apoptosis，which may be related to the up-regulation of miR-124. The level of miR-7 is related to the inhibition of IL-11 expression. |
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