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肿瘤细胞逃避免疫系统并使自身永生的一种方法是bcl—2蛋白的表达,bcl—2能延迟和抑制由p53、Myc、化疗和电离辐射等因素诱发的细胞凋亡(apoptosis)。神经细胞瘤、前列腺癌和某些类型的白血病预后及疗效差与bcl—2的过量表达有关。 美国密执安大学医学院Nunez等发现一种可用于这些癌症的新方法,即抑制细胞凋亡抑制因子bcl—2的作用。此法能选择性地破坏癌性骨髓细胞,而不影响正常造血干细胞,并能重建免疫缺陷小鼠的骨髓。 研究者在研究bcl—2的同系物bcl—x时发现了bcl—x的两种变体bcl—x_L和bcl—x_s。如同bcl—2,bcl—x_L也是一种细胞凋亡抑制因子,然而,研究者发现bcl—x_s在细胞表达bcl—2时能增强细胞凋亡信号,从而抑制bcl—2。为此,研究者构建了一种腺病毒载体以传递bcl—x_s基因至肿瘤细胞中。 用bcl—x_s腺病毒感染6例原发性乳腺癌患者的癌细胞后,即使在很低浓度,亦能观察到显著的细胞毒性。而用仅含标记基因的对照载体感染癌细胞后,对癌细胞生存力无影
One way that tumor cells evade the immune system and immortalizes itself is the expression of bcl-2 protein, which delays and inhibits apoptosis (apoptosis) induced by factors such as p53, Myc, chemotherapy, and ionizing radiation. The poor prognosis and efficacy of neuroblastoma, prostate cancer, and certain types of leukemia are related to overexpression of bcl-2. Nunez et al., of the University of Michigan Medical School in the United States, have discovered a novel method that can be used for these cancers, namely the inhibition of the apoptosis inhibitor bcl-2. This method can selectively destroy cancerous bone marrow cells without affecting normal hematopoietic stem cells and can rebuild the bone marrow of immunodeficient mice. Researchers found bcl-x variants bcl-x_L and bcl-x_s when studying the bcl-2 homolog bcl-x. Like bcl-2, bcl-x_L is also an inhibitor of apoptosis. However, the researchers found that bcl-x_s enhances the apoptosis signal when cells express bcl-2, thereby inhibiting bcl-2. To this end, the researchers constructed an adenoviral vector to deliver the bcl-x_s gene to tumor cells. After infecting the cancer cells of 6 primary breast cancer patients with bcl-x_s adenovirus, significant cytotoxicity was observed even at very low concentrations. Infection of cancer cells with a control vector containing only the marker gene has no effect on the viability of cancer cells.