Thomadaki Hellinida, Scorilas Andreas
Department of Biochemistry and Molecular Biology, Faculty of Biology, University of Athens, Panepistimiopolis, 15701 Athens, Greece.
Ann N Y Acad Sci. 2007 Jan;1095:35-44. doi: 10.1196/annals.1397.005.
Most apoptosis-related genes regulate cellular fate as a response to anticancer drugs. Modulations at the mRNA levels of such genes often correlate with the sensitivity of various types of cancer cells to chemotherapeutic reagents. The drugs cisplatin, carboplatin, and doxorubicin exhibit anticancer activity, the mechanism of which is not yet completely clarified, although they are known to modulate the expression of several genes including apoptosis-related genes, such as members of the BCL2 (Bcl-2) family. In order to define the significance of the expression patterns of such genes as a response to anticancer drug cytotoxic activity, we studied the possible alterations in the mRNA expression levels of various apoptosis-related genes, including the new member, BCL2L12, after cell treatment with distinct anticancer drugs (cisplatin, carboplatin, and doxorubicin), in the breast cancer cell line, MCF-7. The kinetics of cell toxicity was evaluated by the MTT method, whereas the expression levels of distinct apoptosis-related genes were analyzed by reverse transcriptase polymerase chain reaction (RT-PCR), using gene-specific primers. The percentage of nonviable cells was upregulated with increasing concentrations and cell exposure time to the different anticancer drugs. Distinct modulations of apoptosis-related genes, at the mRNA level, were also observed. However, further work is required in order to ascertain whether the mRNA expression profile of such genes may provide evidence for their contribution to more specific and sensitive prediction of breast cancer response to treatment and therefore the rationale for individualized, more appropriate, and successful treatment.
大多数与细胞凋亡相关的基因通过调节细胞命运来响应抗癌药物。这些基因在mRNA水平上的调节通常与各类癌细胞对化疗药物的敏感性相关。顺铂、卡铂和阿霉素具有抗癌活性,尽管已知它们可调节包括凋亡相关基因(如BCL2(Bcl-2)家族成员)在内的多个基因的表达,但其抗癌机制尚未完全阐明。为了确定此类基因的表达模式作为对抗癌药物细胞毒性活性的响应的意义,我们研究了在用不同抗癌药物(顺铂、卡铂和阿霉素)处理乳腺癌细胞系MCF-7后,各种凋亡相关基因(包括新成员BCL2L12)的mRNA表达水平可能发生的变化。通过MTT法评估细胞毒性动力学,而使用基因特异性引物通过逆转录聚合酶链反应(RT-PCR)分析不同凋亡相关基因的表达水平。随着不同抗癌药物浓度的增加和细胞暴露时间的延长,非存活细胞的百分比上调。在mRNA水平上也观察到了凋亡相关基因的不同调节。然而,为了确定此类基因的mRNA表达谱是否可为它们对乳腺癌治疗反应的更特异性和敏感性预测的贡献提供证据,从而为个体化、更合适和成功的治疗提供理论依据,还需要进一步的研究。