长期应用萝卜硫素不会诱导肾癌细胞产生耐药性。
Chronic Sulforaphane Application Does Not Induce Resistance in Renal Cell Carcinoma Cells.
作者信息
Rutz Jochen, Juengel Eva, Euler Stephanie, Maxeiner Sebastian, Justin Saira, Roos Frederik, Chun Felix K-H, Blaheta Roman A
机构信息
Department of Urology, Goethe-University, Frankfurt am Main, Germany.
Department of Urology and Pediatric Urology, University Medical Center Mainz, Mainz, Germany.
出版信息
Anticancer Res. 2018 Nov;38(11):6201-6207. doi: 10.21873/anticanres.12974.
BACKGROUND/AIM: Since the natural compound sulforaphane (SFN) has been shown to stop tumor growth, renal cell carcinoma (RCC) patients often use this drug in addition to their prescribed oncotherapy. The aim of this study was to examine whether resistance to SFN may develop after long-term application.
MATERIALS AND METHODS
Several RCC cell lines were incubated with SFN for short periods of time (24-72 h) or long periods of time (8 weeks) and cell growth, proliferation, and cell-cycle proteins were analyzed.
RESULTS
Both short- and long-term application of SFN distinctly reduced RCC cell growth and proliferation. However, differences in the distribution of cells in each phase of the cell cycle and in the expression of cell-cycle proteins were apparent. Short-term treatment induced S-phase arrest, whereas long-term treatment induced G/G-phase arrest. Expression of Cdk1 and Cdk2 increased over short-term incubation, but decreased long-term. Expression of pCdk2, Akt, and Raptor were reduced following long-term SFN-exposure, but remained unchanged when SFN was applied for short periods of time.
CONCLUSION
Chronic use of SFN did not evoke resistance, but differentially altered signaling pathways, compared to short-term use.
背景/目的:由于天然化合物萝卜硫素(SFN)已被证明可抑制肿瘤生长,肾细胞癌(RCC)患者常在规定的肿瘤治疗之外使用这种药物。本研究的目的是检查长期应用后是否会产生对SFN的耐药性。
材料与方法
将几种RCC细胞系分别与SFN短期(24 - 72小时)或长期(8周)孵育,然后分析细胞生长、增殖及细胞周期蛋白。
结果
短期和长期应用SFN均明显降低RCC细胞的生长和增殖。然而,细胞周期各阶段细胞分布及细胞周期蛋白表达存在明显差异。短期处理诱导S期阻滞,而长期处理诱导G/G期阻滞。短期孵育时Cdk1和Cdk2表达增加,但长期孵育时降低。长期暴露于SFN后,pCdk2、Akt和Raptor的表达降低,但短期应用SFN时保持不变。
结论
与短期使用相比,长期使用SFN不会引起耐药性,但会不同程度地改变信号通路。