成纤维细胞生长因子抑制剂BGJ398对肾癌增殖、粘附和侵袭功能的相关研究

发布时间：2018-06-30 01:02

本文选题：肾癌 + 成纤维细胞生长因子受体抑制剂　；参考：《南方医科大学》2017年硕士论文

【摘要】：FGFRs的异常表达与肿瘤的发生和转移密切相关,但是在肾透明细胞癌中的研究很少。为了研究成纤维细胞生长因子抑制剂对肾细胞癌的影响,本研究设计通过体外实验研究FGFR的特异性抑制剂BGJ398对人源肾癌细胞株OS-RC-2细胞的作用,考察BGJ398对OS-RC-2细胞增殖、粘附及其对细胞侵袭功能的影响,从而初步阐明FGFR信号分子的特异性抑制对肾癌细胞生物学功能的影响,为肾细胞癌的靶向治疗提供新思路。方法用不同浓度0、0.1、0.5、1、2、5、10μmol/L的FGFR抑制剂BGJ398处理体外培养的人源肾癌细胞OS-RC-2后,通过MTT法检测细胞增殖变化;激光共聚焦显微镜观察BGJ398对细胞的活力和骨架的影响;Transwell小室法检测BGJ398对人肾癌细胞侵袭能力的影响。结果BGJ398能明显抑制OS-RC-2细胞增殖。MTT法结果显示BGJ398处理人肾癌细胞后,细胞增殖受到抑制,并具有剂量依赖性,即随药物浓度升高(0～10μmol/L)而抑制作用增强。Live/Dead荧光染色实验证明BGJ398可显著抑制肾癌细胞的增殖及活力(P0.01)。细胞粘附及Transwell实验结果表明,BGJ398可抑制细胞骨架的重塑及侵袭效应(P0.01)。结论BGJ398对肾癌细胞的增殖,活力和侵袭力具有明显的抑制作用。因此,抑制FGFRs有望成为肾癌治疗的新靶点,并且为FGFR特异性抑制剂成为潜在的肾癌靶向治疗药物提供实验证据。
[Abstract]:The abnormal expression of FGFRs is closely related to the occurrence and metastasis of tumor, but little research has been done in clear cell carcinoma of kidney. In order to study the effect of fibroblast growth factor inhibitor on renal cell carcinoma, the effect of BGJ398, a specific inhibitor of FGFR, on human renal cell carcinoma cell line OS-RC-2 was studied in vitro, and the proliferation of OS-RC-2 cell line was investigated by BGJ398. Adhesion and its effect on cell invasion function, so as to clarify the specific inhibition of FGFR signal molecules on the biological function of renal cell carcinoma, and provide a new idea for targeted therapy of renal cell carcinoma. Methods Human renal cancer cell line OS-RC-2 was treated with 10 渭 mol / L FGFR inhibitor BGJ398 at different concentrations of 0. 1, 0. 5 and 0. 5 渭 mol / L, and cell proliferation was detected by MTT assay. The effect of BGJ398 on cell viability and cytoskeleton was observed by laser confocal microscopy. Results BGJ398 could significantly inhibit the proliferation of OS-RC-2 cells. MTT assay showed that BGJ398 could inhibit the proliferation of human renal cancer cells in a dose-dependent manner. That is, with the increase of drug concentration (0 ~ 10 渭 mol / L), the inhibitory effect was enhanced. Live / Dead fluorescence staining showed that BGJ398 could significantly inhibit the proliferation and activity of renal cancer cells (P0.01). The results of cell adhesion and Transwell experiments showed that BGJ398 inhibited the remodeling and invasion of cytoskeleton (P0.01). Conclusion BGJ 398 can inhibit the proliferation, activity and invasion of renal cancer cells. Therefore, the inhibition of FGFRs is expected to be a new target for the treatment of renal cell carcinoma, and provide experimental evidence for FGFR specific inhibitors as potential targeted drugs for renal cell carcinoma.
【学位授予单位】：南方医科大学
【学位级别】：硕士
【学位授予年份】：2017
【分类号】：R737.11

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