| 摘要: |
| ［摘要］ 目的 探讨胰岛素样生长因子2 mRNA结合蛋白1（IGF2BP1）高表达对卵巢癌细胞紫杉醇耐药的影响及其机制。方法 分别通过Kaplan-Meier Plotter数据库和ROC Plotter数据库分析IGF2BP1表达与卵巢癌患者预后和紫杉醇耐药的相关性。选择对紫杉醇敏感的卵巢癌细胞SKOV3和对紫杉醇耐药的卵巢癌细胞SKOV3-R进行实验。转染IGF2BP1过表达慢病毒和空载病毒至SKOV3-R细胞，分别命名为S-R-IGF2BP1-OE细胞和S-R-EV细胞。通过CCK-8实验检测细胞增殖活力，通过实时荧光定量聚合酶链反应（RT-qPCR）检测IGF2BP1 mRNA的表达情况，通过流式细胞术检测细胞周期分布情况，通过Western blot实验检测细胞周期相关因子的表达水平。结果 IGF2BP1高表达与卵巢癌患者较差的总体生存期（OS）和无进展生存期（PFS）显著相关（P<0.05）。化疗耐药组IGF2BP1 mRNA表达水平显著高于敏感组（P<0.05）。SKOV3-R细胞IGF2BP1 mRNA表达水平较SKOV3细胞显著升高（P<0.05）。在紫杉醇干预下，S-R-IGF2BP1-OE细胞的增殖活力较S-R-EV细胞更高（P<0.05），紫杉醇对S-R-IGF2BP1-OE细胞和S-R-EV细胞的半数抑制浓度（IC50）分别为187.02 nmol/L和98.76 nmol/L；S-R-IGF2BP1-OE细胞G0/G1期和G2/M期占比均显著低于S-R-EV细胞（P<0.05）；S-R-IGF2BP1-OE细胞中细胞周期蛋白A2（cyclin A2）表达水平高于S-R-EV细胞，p27激酶抑制蛋白1（p27 KIP1）、p21 CDK相互作用蛋白1（p21 Cip1）、糖原合成酶激酶-3β（GSK-3β）、细胞周期依赖性激酶7（CDK7）表达水平低于S-R-EV细胞，差异有统计学意义（P<0.05）。结论 IGF2BP1高表达与卵巢癌患者不良预后有关，可能通过调控卵巢癌细胞细胞周期介导紫杉醇耐药。 |
| 关键词: 胰岛素样生长因子2 mRNA结合蛋白1 卵巢癌 紫杉醇 耐药 细胞周期 |
| DOI：10.3969/j.issn.1674-3806.2025.11.09 |
| 分类号:R 737.31 |
| 基金项目:国家自然科学基金项目（编号：82260721，81903644）；广西自然科学基金重点项目（编号：2024GXNSFDA010045）；广西区域性高发肿瘤早期防治研究教育部重点实验室项目（编号：GKE-ZZ202148，GKE-ZZ202235） |
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| Study on effects of high expression of IGF2BP1 on paclitaxel-resistant ovarian cancer cells and its mechanisms |
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YU Yue1, CHEN Xiaoying2, LIU Xia2, YIN Fuqiang1
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1.Life Sciences Institute, Guangxi Medical University, Nanning 530021, China; 2.Key Laboratory of Longevity and Aging-Related Diseases of Chinese Ministry of Education, School of Basic Medical Sciences, Guangxi Medical University, Nanning 530021, China
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| Abstract: |
| ［Abstract］ Objective To explore the effects of high expression of insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1) on paclitaxel-resistant ovarian cancer cells and its mechanisms. Methods Kaplan-Meier Plotter database and ROC Plotter database were used to analyze the correlations of IGF2BP1 expression with the ovarian cancer patients′ prognosis and paclitaxel resistance, respectively. The ovarian cancer cell line SKOV3 sensitive to paclitaxel and the ovarian cancer cell line SKOV3-R resistant to paclitaxel were selected for experiment. IGF2BP1-overexpressing lentivirus and empty vector were transfected into SKOV3-R cells, which were named S-R-IGF2BP1-OE cells and S-R-EV cells, respectively. Cell proliferation activity was detected by using CCK-8 assay. The expression of IGF2BP1 mRNA was detected by using reverse transcription-quantitative real-time polymerase chain reaction(RT-qPCR). Cell cycle distribution was detected by using flow cytometry. The expression levels of cell cycle-related factors were detected by using Western blot assay. Results High expression of IGF2BP1 was significantly correlated with worse overall survival(OS) and progression-free survival(PFS) in the ovarian cancer patients(P<0.05). The expression level of IGF2BP1 mRNA in the chemotherapy-resistant group was significantly higher than that in the chemotherapy-sensitive group(P<0.05). The expression level of IGF2BP1 mRNA in SKOV3-R cells was significantly higher than that in SKOV3 cells(P<0.05). Under the intervention of paclitaxel, the proliferation activity of S-R-IGF2BP1-OE cells was higher than that of S-R-EV cells(P<0.05). The half maximal inhibitory concentration(IC50) of paclitaxel for S-R-IGF2BP1-OE cells and the IC50 of paclitaxel for S-R-EV cells were 187.02 nmol/L and 98.76 nmol/L, respectively. The proportions of G0/G1 phase and G2/M phase in S-R-IGF2BP1-OE cells were significantly lower than those in S-R-EV cells(P<0.05). The expression level of cyclin A2 in S-R-IGF2BP1-OE cells was higher than that in S-R-EV cells, and the expression levels of p27 kinase inhibitor protein 1(p27 KIP1), p27 CDK-interacting protein 1(p21 Cip1), glycogen synthase kinase-3β(GSK-3β), and cell cyclin-dependent kinase 7(CDK7) in S-R-IGF2BP1-OE cells were lower than those in S-R-EV cells, and the differences were statistically significant(P<0.05). Conclusion High expression of IGF2BP1 is associated with poor prognosis in ovarian cancer patients, which may mediate paclitaxel resistance by regulating the cell cycle of ovarian cancer cells. |
| Key words: Insulin-like growth factor 2 mRNA-binding protein 1(IGF2BP1) Ovarian cancer Paclitaxel Drug resistance Cell cycle |
