| 冯艳坤,陈治军.酮咯酸通过胰岛素样生长因子 2信号通路抑制卵巢癌的生长和转移[J].安徽医药,2023,27(1):190-194. |
| 酮咯酸通过胰岛素样生长因子 2信号通路抑制卵巢癌的生长和转移 |
| Ketorolac inhibits ovarian cancer growth and metastasis via IGF2 signaling pathway |
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| DOI：10.3969/j.issn.1009-6469.2023.01.041 |
| 中文关键词: 酮咯酸 IGF2信号通路 卵巢肿瘤 迁移 侵袭 免疫印迹法 TraNCwell 小鼠，近交 BALB C |
| 英文关键词: Ketorolac IGF2 signaling pathway Ovarian neoplasms Migration Invasion Western blotting TraNCwell Mice,inbred BALB C |
| 基金项目:国家自然科学基金( 81460177) |
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| 中文摘要: |
| 目的探讨酮咯酸对卵巢癌生长、转移影响及机制。方法实验于 2019年 8月至 2020年 3月进行。细胞计数试剂盒(CCK-8)法检测不同剂量( 0.10 g/L、0.50 g/L、1.00 g/L、1.50 g/L)酮咯酸对人卵巢癌细胞 SKOV3的抑制率，筛选酮咯酸的最佳作用浓度。 SKOV3细胞分为 NC组、酮咯酸组、 DMSO组、 Linsitinib组、酮咯酸 +pcDNA 3.1组和酮咯酸 +pcDNA 3.1-IGF2组， TraNCwell法检测各组细胞迁移和侵袭，蛋白质印迹法( Western blotting)法检测各组细胞中胰岛素样生长因子 2(IGF2)、胰岛素样生长因子 1受体( IGF1R)的蛋白表达。裸鼠分为 NC组和酮咯酸组，每组 10只，观察酮咯酸对肿瘤生长及肿瘤组织中 IGF2、IGF1R的蛋白表达的影响。结果与 NC组相比，不同剂量( 0.10、0.50、1.00、1.50 g/L)酮咯酸组细胞抑制率升高［( 6.99±0.06)%、(23.31±2.11)%、(51.39±6.91)%、(76.14±4.36)%比( 0.02±0.00)%，P <0.05］选择 1.0 g/L酮咯酸为最佳浓度。与 NC组相比，酮咯酸组细胞迁移数［(54±5)个比( 103±9)个］和侵袭数［( 41±4)个比( 76±6)个，］及细胞中 IGF2(0.31±0.03比 1.01±0.06)和 IGF1R蛋白( 0.26±0.02比 0.99±0.08)表达均显著降低(均 P<0.05)。与 NC组或 DMSO组相比， Linsitinib组细胞迁移数［( 63±6)个比( 98±9)个、(99±7)个］和侵袭数［(51±5)个比( 73±6)个、(75±6)个］及细胞中 IGF2(0.28±0.02比 0.98±0.05、1.00±0.07)和 IGF1R(0.29±0.02比 0.99±0.06、1.02±0.08)蛋白表达均显著降低(均 P<0.05)。与酮咯酸组或酮咯酸 +pcDNA 3.1组相比，酮咯酸+pcDNA 3.1-IGF2组细胞迁移数［( 87±7)个比( 52±5)个、(53±5)个］和侵袭数［( 75±6)个比( 44±4)个、(42±4)个］及细胞中 IGF2(1.28±0.13比 0.31±0.03、0.33±0.04)和 IGF1R(1.19±0.12比 0.26±0.02、0.27±0.03)蛋白表达均显著升高(均 P<0.05)。与 NC组相比，酮咯酸组裸鼠肿瘤的质量［( 0.53±0.05)g比( 1.01±0.07)g］和体积［( 0.55±0.05)cm3比( 1.00±0.04)cm3］均显著降低( P<0.05)，肿瘤组织中 IGF2(0.46±0.04比 0.99±0.08)和 IGF1R(0.52±0.05比 0.97±0.09)蛋白表达均显著降低(均 P<0.05)。结论酮咯酸可在体外抑制卵巢癌细胞迁移和侵袭及体内肿瘤生长，其机制可能与抑制 IGF2信号通路有关。 |
| 英文摘要: |
| Objective To investigate the effect of ketorolac on the growth and metastasis of ovarian cancer and its mechanism.Meth? ods Experiments were conducted from August 2019 to March 2020. Cell counting kit (CCK-8) method was used to detect the inhibition rates of ketorolac (0.10 g/L, 0.50 g/L, 1.00 g/L, 1.50 g/L) on human ovarian cancer cell line SKOV3. The optimal concentration ofketorolac was sorted out. Patients were assigned into NC group, ketorolac group, DMSO group, Linsitinib group, ketorolac + pcDNA 3.1group and ketorolac + pcDNA3.1-IGF2 group. Cell migration and invasion were detected by TraNCwell, the protein expressions of insulin-like growth factor 2 (IGF2) and insulin-like growth factor 1 receptor (IGF1R) were detected by western blotting. Nude mice were assigned into NC group and ketorolac group, with 10 in each group. Observation was made of the effect of ketorolac on tumor growth andprotein expressions of IGF2 and IGF1R in tumor tissue.Results Compared with the NC group, the cell inhibition rates of ketorolacgroups at different doses (0.10 g/L, 0.50 g/L, 1.00 g/L, 1.50 g/L) increased [(6.99±0.06) %, (23.31±2.11) %, (51.39±6.91) %, (76.14±4.36) % vs. (0.02±0.00) %, P<0.05], and 1.00 g/L of ketorolac was selected as the best concentration. Compared with the NC group, thenumber of cell migration [(54±5) vs. (103±9)], the number of invasion [(41±4) vs. (76±6)] and the protein expressions of IGF2 [(0.31± 0.03) vs. (1.01±0.06)] and IGF1R [(0.26±0.02) vs. (0.99±0.08)] in the ketorolac groups were significantly reduced (all P<0.05). Compared with the NC group or the DMSO group, the number of cell migration [(63±6) vs. (98±9), (99±7)], the number of invasion [(51±5) vs. (73±5), (75±6)] and the protein expressions of IGF2 [(0.28±0.02) vs. (0.98±0.05), (1.00±0.07)] and IGF1R [(0.29±0.02) vs. (0.99± 0.06), (1.02±0.08)] in the Linsitinib group were significantly reduced (all P<0.05). Compared with the ketorolac group or the ketorolac+pcDNA 3.1 group, the number of cell migration [(87±7) vs. (52±5), (53±5)], the number of cell invasion [(75±6) vs. (44±4), (42±4)] and the protein expressions of IGF2 [(1.28±0.13) vs. (0.31±0.03), (0.33±0.04)] and IGF1R [(1.19±0.12) vs. (0.26±0.02), (0.27±0.03)] in the ketorolac+pcDNA 3.1-IGF2 group were significantly increased (all P<0.05). Compared with the NC group, the weight [(0.53±0.05) g vs. (1.01±0.07) g] and volume [(0.55±0.05) cm3 vs. (1.00±0.04) cm3] of the nude mouse tumors in the ketorolac group were significantly reduced (both P<0.05), and the protein expressions of IGF2 [(0.46±0.04) vs. (0.99±0.08)] and IGF1R [(0.52±0.05) vs. (0.97±0.09)] in tumor tissue were significantly reduced (both P<0.05).Conclusion Ketorolac can inhibit the migration and invasion of ovarian cancercells in vitro and tumor growth in vivo, and its mechanism may be related to the inhibition of IGF2 signaling pathway. |
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