| 盛 天,冯佳薪,安丽君,邹 羽,张 磊.RECK基因在维莫非尼抑制皮肤黑素瘤增殖过程中的作用[J].,2024,(21):4028-4034 |
| RECK基因在维莫非尼抑制皮肤黑素瘤增殖过程中的作用 |
| Role of the RECK Gene in the Inhibition of Cutaneous Malignant Melanoma Proliferation by Vemurafenib |
| 投稿时间：2024-05-24 修订日期：2024-06-18 |
| DOI：10.13241/j.cnki.pmb.2024.21.005 |
| 中文关键词: 皮肤黑素瘤 RECK基因 维莫非尼 增殖 |
| 英文关键词: Cutaneous malignant melanoma RECK gene Vemurafenib Proliferation |
| 基金项目:贵州省科技计划项目（黔科合基础-ZK[2024]一般591） |
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| 中文摘要: |
| 摘要 目的：探讨半胱氨酸丰富蛋白Kazal基元（RECK）基因在维莫非尼抑制皮肤黑素瘤（CMM）增殖的过程中的作用。方法：通过生物信息学分析验证RECK基因在CMM组织和癌旁组织中的表达，根据RECK基因在CMM组织中的表达情况将样本分为低表达组和高表达组。Kaplan-Meier生存曲线分析RECK基因低表达组和高表达组间的差异。采用人恶性黑素瘤A375细胞构建裸鼠移植瘤模型，当肿瘤体积长到约100 mm3时，将荷瘤小鼠分为维莫非尼组（75 mg/kg/day灌胃）、对照组（等量溶剂灌胃），每组各为6只。治疗结束后采集CMM组织，采用实时荧光定量PCR法检测并比较维莫非尼组和对照组RECK基因的mRNA表达水平差异，采用蛋白免疫印迹法和免疫组织化学染色的方法检测并比较维莫非尼组和对照组RECK蛋白表达水平的差异。结果：生物信息学分析发现，RECK基因在CMM组织中的表达水平较癌旁组织明显降低，差异具有统计学意义（P＜0.001）。Kaplan-Meier生存曲线分析显示，RECK基因表达水平与CMM患者预后具有相关性，RECK基因低表达组生存时间小于高表达组（P=0.007）。连续给药16天后，维莫非尼组的相对肿瘤增殖率为37.60%，抑瘤率为63.45%，成功构建CMM裸鼠移植瘤抑制模型。维莫非尼组和对照组的RECKmRNA相对量分别为1.02±0.13、0.99±0.15，差异无统计学意义（P＞0.05）；维莫非尼组和对照组的RECK蛋白表达分别为0.19±0.01、0.18±0.01，差异无统计学意义（P＞0.05）；免疫组织化学染色显示，RECK基因在维莫非尼组和对照组中均呈阴性表达。结论：RECK基因与CMM的发展及预后具有相关性，但在维莫非尼抑制CMM增殖的过程中 RECK无明显变化。 |
| 英文摘要: |
| ABSTRACT Objective: To explore the role of the reversion inducing cysteine rich protein with Kazal motifs(RECK) gene in inhibiting of cutaneous malignant melanoma(CMM) proliferation by vemurafenib. Methods: The expression of RECK gene in CMM tissue and adjacent tissue was verified through bioinformatics analysis, and divided the sample into low expression and high expression groups based on the expression of RECK gene in CMM tissue. The differences between the RECK gene low expression group and the high expression group were analysed by Kaplan Meier survival curve. Human malignant melanoma A375 cells were used to construct a nude mouse transplanted tumor model. When the tumor volume reached about 100 mm3, the tumor-bearing mice were divided into vemurafenib group (75 mg/kg/day gavage) and the control group (equal amount of solvent gavage), with 6 mice in each group. After treatment, CMM tissue was collected, and real-time fluorescence quantitative PCR was used to detect and compare the mRNA expression levels of RECK gene between the verbenib group and the control group. Western blot and immunohistochemical staining were used to detect and compare the differences in RECK protein expression levels between the remofenib group and the control group. Results: Bioinformatics analysis showed that the expression level of RECK gene in CMM tissues was significantly lower than that in adjacent tissues, with statistical significance(P<0.001). Kaplan Meier survival curve analysis showed that the level of RECK gene expression was correlated with the prognosis of CMM patients, the survival time of the RECK gene low expression group was shorter than that of the high expression group (P=0.007). After 16 consecutive days of administration, the relative tumor proliferation rate and tumor inhibition rate of the vemurafenib group were 37.60% and 63.45%, respectively, and successfully constructed a CMM nude mouse tumor inhibition model for transplantation. The relative amounts of RECK mRNA in the vemurafenib group and the control group were 1.02±0.13 and 0.99±0.15, respectively, with no statistically significant difference (P>0.05); The expression of RECK protein in the vemurafenib group and the control group was 0.19±0.01 and 0.18±0.01, respectively, with no statistically significant difference (P>0.05); Immunohistochemical staining showed that the RECK gene was negatively expressed in both the vemurafenib group and the control group. Conclusion: The RECK gene is correlated with the development and prognosis of CMM, but there is no significant change in RECK during the inhibition of CMM proliferation by veimofenib. |
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