Objective To study the effect of 5-fluorouracil (5-FU) induced apoptosis of the rectal carcinoma cell line HR8348 in vitro and the relationship between apoptosis induced by 5-FU and the expression of bcl-2，bcl-xl，bax and p53,and to investigate the possible mechanism of apoptosis of rectal carcinoma cell line HR8348 induced by 5-FU.Methods After treatment with 5-FU for 24 h,the apoptotic index was detected by methyl green and pyronine Y staining and by terminal deoxynucleotidyl transferase (TdT)mediated dUTP nick end labeling (TUNEL).The bcl-2,bcl-xl,bax and p53 gene expression of HR8348 cells were examined by immunohistochemical method.Results After treatment with 5-FU,the apoptotic index of experiment group was significantly increased,there was significant difference as compared with the control.Exposed to 5-FU for 12 h,24 h and 36 h,the expression of bcl-2 of HR8348 cell line remained unchanged,but the expression of bcl-xl slightly diminished,while the expression of bax was remarkly increased,the expression of p53 was not detected in both experiment and control groups.Conclusion This results indicate that 5-FU may induce apoptosis of rectal carcinoma cell line HR8348 and the possible mechanism of apoptosis induction is through upregulation of bax expression and the change of bax to bcl-xl ratio.
Citation：
JI Fengcun,CHENG Ruochuan,KANG Junsheng. Induction of Apoptosis of Rectal Carcinoma Cell Line HR8348 by 5-Fluorouracil in Vitro. CHINESE JOURNAL OF BASES AND CLINICS IN GENERAL SURGERY, 2003, 10(6): 564-567. doi:
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- 1. 姜泊主编. 细胞凋亡基础与临床 [M]. 第1版. 北京： 人民卫生出版社， 1999∶257～259.
- 2. Sinicrope FA,Ruan SB,Cleary KR,et al. bcl2 and p53 oncoprotein expression during colorectal tumorigenesis [Ｊ].Cancer Res, 1995; 55(2)∶237.
- 3. 郁宝铭， 郑民华， 王灏， 等. p53基因在5氟尿嘧啶致大肠肿瘤细胞凋亡的影响 [Ｊ]. 中国癌症杂志, 1998; 8（4）∶243.
- 4. Koshiji M,Adachi Y,Taketani S,et al.Mechanisms underlying apoptosis induced by combination of 5fluorouracil and interferongamma [Ｊ].Biochem Biophys Res Commun, 1997; 240(2)∶376.
- 5. 骆成玉， 李世拥. 大肠癌bcl2基因表达和重排的研究 [Ｊ]. 中国普外基础与临床杂志， 1999； 6（1）∶4.
- 6. Yang E,Korsmeyer SJ.Molecular thanatopsis: a discourse on the bcl2 family and cell death [Ｊ].Blood, 1996; 88(2)∶386.
- 7. Huang DC,Cory S, Strasser A. bcl2,bclxl and adenovirus protein EIB19kD are functionally equivalent in their ability to inhibit cell death [Ｊ].Oncogene, 1997; 14(4)∶405.
- 8. Sedlak TW,Oltvai ZN,Yang E,et al.Multiple bcl2 family members demonstrate selective dimerization with bax [Ｊ].Proc Natl Acad Sci USA， 1995； 92(17)∶7834.
- 9. Nita ME,Nagawa H, Tominaga O,et al.5Fluorouracil induces apoptosis in human colon cancer cell lines with modulation of bcl2 family proteins [Ｊ]. Br J Cancer， 1998; 78(8)∶986.
- 10. Schneider HJ,Sampson SA,Cunningham D,et al. bcl2 expression and response to chemotherapy in colorectal adenocarcimomas [Ｊ].Br J Cancer, 1997; 75(3)∶427.
- 11. Waston AJ,Merritt AJ,Jones LS, et al.Evidence for reciprocity of bcl2 and p53 expression in human colorectal adenomas and carcinomas [Ｊ].Br J Cancer, 1996; 73(8)∶889.
- 12. Soussi T.The p53 tumor suppressor gene: from molecular biology to clinical investigation [Ｊ]. Ann N Y Acad Sci, 2000; 910∶121.
- 13. Silvestrini R,Veneroni S,Daidone MG,et al.The bcl2 protein:a prognostic indicator strongly related to p53 protein in lymph nodenegative breast cancer patients [Ｊ].J Natl Cancer Inst, 1994; 86(7)∶499.
