术前介入化疗后直肠癌细胞凋亡和增殖改变与转化生长因子β1表达的相关性研究

Relativity Between the Expression of Transforming Growth Factor Betal and the Apoptosis and Proliferation of Rectal Cancer Cell after Preoperative Transarterial Chemotherapy

目的探讨转化生长因子β1(TGFβ1)在直肠癌术前介入化疗后与肿瘤细胞凋亡和增殖改变的关系。方法32例直肠癌患者术前经供血动脉灌注5氟脲嘧啶、丝裂霉素和表阿霉素,分别于化疗前、化疗后1、23天和7～10天取直肠癌组织,免疫组织化学法检测TGFβ1和增殖细胞核抗原(PCNA)的表达,TUNEL法检测凋亡细胞。结果化疗后TGFβ1灰度值持续升高,化疗后7～10天升至27.11,明显高于化疗前(13.34);细胞增殖指数(PI)在化疗后第2天明显降低(38.88%),然后逐渐升高,化疗后7～10天较化疗前增高(62.70%),化疗后第1天凋亡指数(AI)显著升高(20.07‰),随后逐渐缓慢下降,但化疗后7～10天仍高于化疗前(11.79‰)。TGFβ1灰度值与PI值呈明显正相关(γ=0.54,P<0.01),而与AI值无关(γ=0.02,P>0.05)。结论介入化疗后7～10天内药物能持续诱导直肠癌细胞凋亡,但随着时间推移,其诱导作用减弱;而癌细胞增殖在化疗后2天内暂时受抑制,然后逐渐变活跃。TGFβ1参与促进化疗后直肠癌细胞增殖,而与化疗诱导直肠癌细胞凋亡无关。

Objective To investigate the relativity between the expression of trans forming growth factor beta1(TGF-β1) and the apoptosis and proliferation of tumor cells after preoperative transarterial chemotherapy in colorectal cancer.Methods 32 cases with rectal cancer received transarterial chemotherapy(5-fluorouracil,mitomycin and epirubicin).Tumor tissue biopsy was performed before chemotherapy and 1、2、3 days and 7～10 days after chemotherapy.The expression of TGF-β1 and proliferating cells nuclear antigen(PCNA) were detected by immunohistologic staining.Cell apoptosis was examined by terminal deoxynucleotidyl transferase(TdT) mediated dUTP-fluorescein and labeling.Results The expression of TGF-β1 was kept increasing after chemotherapy and finally reached 27.11 on the 7th to 10th day after chemotherapy,which was much higher than that before chemotherapy(27.11 vs.13.34).PCNA index(PI) decreased by 38.88% on the second day after chemotherapy,but increased after that.PI increased by 62.70% on the 7th～10th day after chemotherapy,compared with that before chemotherapy.The apoptosis index(AI) increased markedly one day after chemotherapy(20.07‰),then reduced gradually,but it was still higher 7 to 10 days after chemotherapy than before chemotherapy.TGF-β1 was positively correlated with PI(γ=0.54,P<0.01),but not with AI(γ=0.02,P>0.05).Conclusion The preoperative chemotherapy could induce apoptosis of rectal cancer cell within 7 to 10 days after transarterial chemotherapy,but the inducing effect decreased gradually after chemotherapy.However,the cancer cell proliferation is inhibited in 2 days after chemotherapy,then resumes active.TGF-β1 may play a role in the promotion of the proliferation of tumor cell after chemotherapy,but it isn't correlated with apoptosis of tumor cell.