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成纖維細(xì)胞生長因子抑制劑BGJ398對腎癌增殖、粘附和侵襲功能的相關(guān)研究

發(fā)布時間:2018-06-30 01:02

  本文選題:腎癌 + 成纖維細(xì)胞生長因子受體抑制劑 ; 參考:《南方醫(yī)科大學(xué)》2017年碩士論文


【摘要】:FGFRs的異常表達(dá)與腫瘤的發(fā)生和轉(zhuǎn)移密切相關(guān),但是在腎透明細(xì)胞癌中的研究很少。為了研究成纖維細(xì)胞生長因子抑制劑對腎細(xì)胞癌的影響,本研究設(shè)計通過體外實驗研究FGFR的特異性抑制劑BGJ398對人源腎癌細(xì)胞株OS-RC-2細(xì)胞的作用,考察BGJ398對OS-RC-2細(xì)胞增殖、粘附及其對細(xì)胞侵襲功能的影響,從而初步闡明FGFR信號分子的特異性抑制對腎癌細(xì)胞生物學(xué)功能的影響,為腎細(xì)胞癌的靶向治療提供新思路。方法用不同濃度0、0.1、0.5、1、2、5、10μmol/L的FGFR抑制劑BGJ398處理體外培養(yǎng)的人源腎癌細(xì)胞OS-RC-2后,通過MTT法檢測細(xì)胞增殖變化;激光共聚焦顯微鏡觀察BGJ398對細(xì)胞的活力和骨架的影響;Transwell小室法檢測BGJ398對人腎癌細(xì)胞侵襲能力的影響。結(jié)果BGJ398能明顯抑制OS-RC-2細(xì)胞增殖。MTT法結(jié)果顯示BGJ398處理人腎癌細(xì)胞后,細(xì)胞增殖受到抑制,并具有劑量依賴性,即隨藥物濃度升高(0~10μmol/L)而抑制作用增強。Live/Dead熒光染色實驗證明BGJ398可顯著抑制腎癌細(xì)胞的增殖及活力(P0.01)。細(xì)胞粘附及Transwell實驗結(jié)果表明,BGJ398可抑制細(xì)胞骨架的重塑及侵襲效應(yīng)(P0.01)。結(jié)論BGJ398對腎癌細(xì)胞的增殖,活力和侵襲力具有明顯的抑制作用。因此,抑制FGFRs有望成為腎癌治療的新靶點,并且為FGFR特異性抑制劑成為潛在的腎癌靶向治療藥物提供實驗證據(jù)。
[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.
【學(xué)位授予單位】:南方醫(yī)科大學(xué)
【學(xué)位級別】:碩士
【學(xué)位授予年份】:2017
【分類號】:R737.11

【參考文獻(xiàn)】

相關(guān)期刊論文 前2條

1 惠琦;李校X;王曉杰;;成纖維細(xì)胞生長因子的臨床轉(zhuǎn)化及相關(guān)新藥研究進(jìn)展[J];藥學(xué)進(jìn)展;2015年10期

2 張志華;劉鵬;王麗紅;王陶然;薛倩;郝長來;;bFGF表達(dá)對裸鼠白血病移植瘤血管新生影響的研究[J];中國腫瘤臨床;2013年14期

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