BCL-2基因表达与乳腺癌抗凋亡及免疫耐受的关系

Expression of BCL-2 in MCF-7 Cells:a Mechanism for Apoptosis Antagonism and Immune Evasion in Breast Cancer Cells

目的 观察乳腺癌细胞株BCL - 2基因表达与其耐受肿瘤浸润淋巴细胞 (TIL)免疫攻击的关系 ,探索应用BCL- 2硫代反义寡核苷酸 (BCL - 2SON)治疗乳腺癌的途径 .方法 BCL - 2硫代反义寡核苷酸处理乳腺癌细胞株MCF - 7,Western印迹法观察其对BCL - 2表达的抑制 ;并将MCF - 7细胞与乳腺癌标本分离出来的TIL共同培养 ,通过JAM试验观察TIL诱导MCF - 7细胞凋亡的情况 .结果 BCL - 2SON处理的MCF - 7细胞无BCL - 2表达 ,并在JAM试验中随着TIL浓度增加 ,凋亡细胞也增加 ;未经处理的对照组可见BCL - 2表达 ,JAM试验中随着TIL浓度增加 ,凋亡细胞的量无明显变化 .结论 BCL - 2表达的乳腺癌细胞可对抗肿瘤浸润淋巴细胞的免疫攻击 ,BCL - 2SON可作为治疗乳腺癌的新途径 .

Objective In this study, we aim to observe BCL-2 expression and its correlation with apoptosis antagonism, as well as immune evasion of breast cancer cell line. Besides, we further evaluate BCL-2 oligonucleotide in gene therapy for breast cancers. Methods MCF-7 cell line was treated with BCL-2 oligonucleotide and Western blotting was engaged to detect BCL-2 expression. Such MCF-7 cells were then cocultured with TILs isolated from fresh tumor samples and their apoptosis was assessed by JAM test. Results Western blotting revealed that BCL-2 expression in MCF-7 cells was obviously inhibited when treated with its oligonucleotide. Apoptosis of MCF-7 treated with BCL-2 oligonucleotide increased with the elevation of TIL ratio assessed by JAM test, while such phenomenon was not observed in the control group. Conclusions Breast cancer cells expressing BCL-2 may protect them from antitumor immune attack in hosts. BCL-2 oligonucleotide can be used as an effective alternative in gene therapy of breast cancers.