术前动脉灌注化疗联合热疗对晚期乳腺癌细胞凋亡及相关基因表达的影响

Influence of preoperative intra-arterial chemotherapy combined with thermotherapy on apoptosis of cancer cells and apoptosis-related gene in advanced breast cancer

目的探讨术前动脉灌注化疗联合热疗对晚期乳腺癌的疗效以及肿瘤细胞凋亡和凋亡相关基因表达的影响。方法 42例晚期乳腺癌行术前动脉灌注化疗联合热疗,评价其治疗效果。取治疗前穿刺活检组织和治疗后手术切除组织,以TUNEL法检测癌细胞凋亡情况,采用免疫组化方法检测bcl-2、bax蛋白的表达。结果术后常规病理检查均发现肿瘤组织中癌细胞核固缩、碎裂,呈空泡状,胞质变性,细胞间质水肿,细胞坏死及玻璃样变性,炎性细胞浸润,纤维组织增生,血管膜增生,血栓形成。临床完全缓解(CR)16例,占38.10%;部分缓解(PR)20例,占47.62%;病情稳定(SD)6例,占14.29%。乳腺癌细胞凋亡指数(AI)治疗前为6.21%±1.87%,治疗后为17.68%±2.68%,差异有统计学意义(P<0.01)。CR患者AI平均值为22.26%,PR患者AI平均值为12.41%,与治疗前比较差异有统计学意义(P<0.05)。bcl-2蛋白表达水平在治疗前为2.42±0.36,治疗后为1.15±0.06,bax蛋白水平表达在治疗前为0.38±0.04,治疗后为0.95±0.11,治疗前后比较均有统计学差异(P<0.01)。bcl-2、bax平均值CR患者分别为0.89、1.08,PR患者分别为1.43、0.82,与治疗前比较差异均有统计学意义(P<0.05)。结论术前动脉灌注化疗联合热疗能诱导乳腺癌细胞凋亡相关基因的表达,促进癌细胞凋亡,影响临床疗效。

Objective To investigate the curative effect and influence of preoperative arterial chemotherapy combined with thermotherapy on therapeutive effect,apoptosis of cancer cells and apoptosis-related genes in advanced breast cancer.Methods Forty-two patients with advanced breast cancer underwent the treatment of preoperative arterial chemotherapy combined with thermotherapy,and the clinical effect was evaluated.Apoptotic cells were examined with TUNEL,and the expressions of bcl-2 and bax in breast cancer were detected by immunohistochemical method before and after treatment.Results The routine pathological examination after operation revealed that there were karyopyknosis,disintegration and vacuolization of tumor cells,and apomorphosis of cytoplasm.There were also intercellular edema,necrosis,hyalinization,inflammatory cell infiltration,fibroplasias,endothelial thickening and thrombosis.Complete remission（CR） was found in 16 cases（38.1%）,partial remission in 20 cases（47.6%）,and stabilization of disease（SD） in 6 cases（14.3%）.Apoptotic index（AI） of breast cancer cells before the treatment was 6.21%±1.87%,significantly lower than that after the combined treatment（17.68%±2.68%,P0.01）.The mean value of AI in CR and PR was 22.26% and 12.41%,respectively,and they were significantly higher than AI of breast cancer before treatment（P0.05）.The expression of bcl-2 before treatment was 2.42±0.36,and it was 0.95±0.11 after combined treatment.The expression of bax before treatment was 0.38±0.04,and it was 0.95±0.11 after combined treatment.There was significant difference between pre-and post-treatment in the expressions of bcl-2 and bax（P0.01）.The expression of bcl-2 and bax was 0.89,1.08 in CR and 1.43,0.82 in PR,respectively.The expressions of bcl-2 in CR and PR were significantly lower than that of pre-treatment,while the expressions of bax in CR and PR were significantly higher than that of pre-treatment（P0.01）.Conclusion Preoperative intra-arterial infusion chemotherapy combined with thermotherapy may induce the expression of bcl-2/bax genes,promote the apoptosis of cancer cells,and raise therapeutic effectiveness in advanced breast cancer.