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目的探讨氟尿嘧啶(5-FU)对结直肠癌细胞G1/S期进程和周期调控的影响;并观察治疗结果是否有药物剂量依赖性。方法采用细胞周期同步化方法,观察结直肠癌化疗主要药物5-FU对人结直肠癌细胞CA-ⅡG1/S期进程的影响,并探讨不同的区域化疗药物浓度与肿瘤杀伤作用的量效关系;并通过RT-PCR方法检测癌细胞在该时期内P16/cyclinD1/CDK4/Rb调控途径转录水平的改变。结果5-FU能够明显延长CA-Ⅱ细胞G1/S期的进程,阻抑细胞周期进展,其阻抑程度对5-FU有剂量依赖性;5-FU同时还可引起癌细胞G1/S期P16基因的转录增强,cyclinD1基因的转录减弱。结论高浓度药物所产生的细胞周期G1/S期阻滞作用可能是5-FU杀伤结直肠癌细胞的机制之一。
Objective To investigate the effect of 5-fluorouracil (5-FU) on the G1 / S phase and the cycle regulation of colorectal cancer cells, and to observe whether the drug treatment dose-dependently. Methods The cell cycle synchronization method was used to observe the effect of 5-FU, a major drug for colorectal cancer chemotherapy, on the course of CA-Ⅱ G1 / S phase in human colorectal cancer cells and to explore the dose-response relationship between the concentration of different regional chemotherapy drugs and the tumor killing effect ; And the change of P16 / cyclinD1 / CDK4 / Rb pathway in cancer cells was detected by RT-PCR. Results 5-FU could significantly prolong the G1 / S phase of CA-Ⅱ cells and inhibit the progression of cell cycle. The inhibition of 5-FU was dose-dependent. 5-FU also induced G1 / S phase P16 gene transcription increased, cyclinD1 gene transcription decreased. Conclusion The cell cycle G1 / S arrest induced by high concentration of drugs may be one of the mechanisms of 5-FU killing colorectal cancer cells.