Molecular Effects of Treatment of Human Colorectal Cancer Cells with Natural and Classical Chemotherapeutic Drugs: Alterations in the Expression of Apoptosis-related BCL2 Family Members, Including BCL2L12
Molecular Effects of Treatment of Human Colorectal Cancer Cells with Natural and Classical Chemotherapeutic Drugs: Alterations in the Expression of Apoptosis-related BCL2 Family Members, Including BCL2L12
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DOI：
10.2174/1389201019666181112101410
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发表时间：
2018-01-01
影响因子：
2.8
通讯作者：
Scorilas, Andreas
中科院分区：
文献类型：
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作者：
Kontos, Christos K.;Avgeris, Margaritis;Scorilas, Andreas
背景资料：目前用于治疗结直肠癌（CRC）的化疗方案包括奥沙利铂、伊立替康和氟尿嘧啶沿着甲酰四氢叶酸。Cytotoxicity involves the induction of programmed cell death.Objective：本研究的目的是评估多柔比星（天然产物柔红霉素的14-OH衍生物）和常见化疗药物（在临床实践中用于治疗CRC）对BCL 2家族的最突出成员，即BCL 2、BAX、BCLX和MCL 1的表达的分子效应。此外，我们试图定义BCL 2L 12，BCL 2家族的另一个成员的作用，其中的凋亡作用是ambiguous.Methods：MTT细胞增殖试验，以确定在72小时的治疗Caco-2和DLD-1结直肠腺癌细胞系的每种化疗药物的IC 50。Real-time PCR用于定量抗凋亡BCL 2-α，BLCX-L和MCL 1-L的转录，促凋亡的BAX，BLCX-S，BLCX-ES，MCL 1-S和MCL 1-ES的转录，和BCL 2L 12的表达与GAPDH mRNA水平的关系。研究BCL 2家族基因和/或特定转录物的表达水平的显着改变observed.Conclusion：内在的凋亡途径被激活，在治疗过程中的CRC细胞与常见的化疗药物。此外，BCL 2L 12 mRNA表达在治疗期间逐渐增加，类似于其他BCL 2家族基因的表达，其有利于细胞凋亡和/或特定的促细胞凋亡转录物，从而表明BCL 2L 12在化疗治疗的CRC细胞中的促细胞凋亡作用。
Background: Current chemotherapy regimens for the treatment of colorectal cancer (CRC) include oxaliplatin, irinotecan, and fluorouracil along with leucovorin. Cytotoxicity involves the induction of programmed cell death.Objective: The purpose of this study was to assess the molecular effects of doxorubicin (a 14-OH derivative of the natural product daunorubicin) and common chemotherapeutic drugs (used in the clinical practice to treat CRC) on the expression of the most prominent members of the BCL2 family, namely BCL2, BAX, BCLX, and MCL1. Moreover, we sought to define the role of BCL2L12, another member of the BCL2 family, the apoptotic role of which is ambiguous.Methods: The MTT cell proliferation assay was used to determine the IC50 of each chemotherapeutic drug at 72 hours of treatment of Caco-2 and DLD-1 colorectal adenocarcinoma cell lines. Real-time PCR was used to quantify the antiapoptotic BCL2-alpha, BLCX-L, and MCL1-L transcripts, the proapoptotic BAX, BLCX-S, BLCX-ES, MCL1-S, and MCL1-ES transcripts, and BCL2L12 expression in relation to GAPDH mRNA levels.Results: We constructed growth curves of Caco-2 and DLD-1 cells and determined the IC50 of each drug at 72 hours of treatment. Significant alterations in the expression levels of the studied BCL2 family genes and/or particular transcripts were observed.Conclusion: The intrinsic apoptotic pathway is activated during treatment of CRC cells with common chemotherapeutic drugs. Moreover, BCL2L12 mRNA expression increases progressively during treatment, similarly to the expression of other BCL2 family genes favoring apoptosis and/or particular proapoptotic transcripts, thus suggesting a proapoptotic role for BCL2L12 in chemotherapy-treated CRC cells.