PDF(Pubmed)
Abstract：
B-cell lymphoma/leukemia gene-2 (Bcl-2) is the primary proto-oncogene that has been shown to work by preventing apoptosis/programmed cell death. Bcl-2 combines a variety of cell-generated signals associated to the survival and death of cells. In glioma, lung, and breast cancer, Bcl-2 over-expression has been linked to an increase in invasion and migration. Many treatment regimens that target Bcl2 have been established and approved, and thus increasing the survival rates of the patients. The primary goal of this research was to recognize new therapeutic compounds that target Bcl2 and assess Bcl2 expression pattern in BC patients. We used various bioinformatic tools as well as several in vitro assays to look out the expression and inhibition of Bcl2 in BC. Our study depicted that Bcl2 had a strong connection with tumour stroma, notably with suppressor cells originating from myeloid tissues. Moreover, in vitro and in silico research identified Paclitaxel as a promising natural substance that targets Bcl2. Overall, this work shows that Bcl2 overexpression accelerates the development of BC, and that targeting Bcl2 in combination with other drugs will dramatically improve BC patient\'s response to treatment and prevent the emergence of drug resistance.
摘要：
B细胞淋巴瘤/白血病基因2（Bcl-2）是主要的原癌基因，已被证明通过防止凋亡/程序性细胞死亡而起作用。Bcl-2结合了与细胞存活和死亡相关的多种细胞产生的信号。在神经胶质瘤中，肺，和乳腺癌，Bcl-2的过表达与侵袭和迁移的增加有关。已经建立并批准了许多针对Bcl2的治疗方案，从而提高患者的生存率。这项研究的主要目标是识别靶向Bcl2的新治疗化合物，并评估BC患者的Bcl2表达模式。我们使用各种生物信息学工具以及几种体外测定来观察Bcl2在BC中的表达和抑制。我们的研究表明，Bcl2与肿瘤基质有很强的联系，特别是来自骨髓组织的抑制细胞。此外，体外和计算机研究确定紫杉醇是靶向Bcl2的有前途的天然物质。总的来说,这项工作表明，Bcl2过表达加速了BC的发展，靶向Bcl2与其他药物联合使用将显著改善BC患者对治疗的反应并防止耐药性的出现。
