Sakakura C, Sweeney E A, Shirahama T, Igarashi Y, Hakomori S, Nakatani H, Tsujimoto H, Imanishi T, Ohgaki M, Ohyama T, Yamazaki J, Hagiwara A, Yamaguchi T, Sawai K, Takahashi T
The First Department of Surgery, Kyoto Perfectural University of Medicine, Kyoto, Japan.
Int J Cancer. 1996 Jul 3;67(1):101-5. doi: 10.1002/(SICI)1097-0215(19960703)67:1<101::AID-IJC17>3.0.CO;2-H.
Resistance to apoptosis plays an important role in tumors that are refractory to chemotherapy and ionizing radiation (IR). bax, which forms a heterodimer with bcl-2 and accelerates apoptosis, is not, or only weakly, expressed in most human breast cancer cells, and weak bax expression is considered to be related to the resistance of breast cancer cells to apoptosis. bax expression vector was introduced to human breast cancer MCF-7 cells, which exhibit weak expression of bax, to demonstrate its role of modulating radiation-induced apoptosis. bax overexpression in MCF-7 cells by stable transfection does not affect viability by itself, but each stable transfectant was more sensitive to IR than the parental MCF-7 cells. The degree of enhancement in radiosensitivity was dependent on the expression level of bax. IR upregulated p53 and p21WAF1 about 5- to 10-fold and downregulated bcl-2 and bcl-XL by 80-90% at 6 hr in both parent and bax stably transfected MCF-7 cells to the same degree. FACS analysis and DNA electrophoresis revealed that this sensitization was due to apoptosis. We suggest that exogenous bax expression might be one of the factors determining cellular radiosensitivity in MCF-7 breast cancer cells and may have therapeutic applications for enhancing radiation sensitivity in breast cancer cells.
对凋亡的抗性在对化疗和电离辐射（IR）难治的肿瘤中起重要作用。bax与bcl-2形成异源二聚体并加速凋亡，在大多数人乳腺癌细胞中不表达或仅微弱表达，并且bax弱表达被认为与乳腺癌细胞对凋亡的抗性有关。将bax表达载体导入bax表达微弱的人乳腺癌MCF-7细胞，以证明其在调节辐射诱导的凋亡中的作用。通过稳定转染使MCF-7细胞中bax过表达本身并不影响细胞活力，但每个稳定转染子对IR的敏感性均高于亲代MCF-7细胞。放射敏感性增强的程度取决于bax的表达水平。在亲代和bax稳定转染的MCF-7细胞中，IR在6小时时均使p53和p21WAF1上调约5至10倍，并使bcl-2和bcl-XL下调80-90％，下调程度相同。FACS分析和DNA电泳显示这种致敏作用是由于凋亡所致。我们认为外源性bax表达可能是决定MCF-7乳腺癌细胞放射敏感性的因素之一，并且可能在增强乳腺癌细胞放射敏感性方面具有治疗应用价值。
