Department of Biochemistry and Molecular Biology, National and Kapodistrian University of Athens, Athens, Greece.
Curr Pharm Biotechnol. 2018;19(13):1076-1086. doi: 10.2174/1389201019666181112103204.
Treatment of cancer with natural chemotherapeutic agents induces apoptosis along with remarkable alterations in the expression of apoptosis-related genes. Deregulation of microRNA (miRNA) expression is implicated in several human malignancies. Vinca alkaloids compose a class of antimitotic drugs preventing cancer cells from dividing, leading to apoptosis. They are commonly used in clinical practice for breast cancer treatment.
The present study focused on the effects of vinca alkaloids (vincristine, vinblastine, and vinorelbine) on miRNA expression of treated breast cancer cells.
We investigated the effect of vincristine, vinblastine, and vinorelbine on the expression of oncogenic and tumor-suppressive miRNAs (miR-15a-5p, miR-16-5p, miR-21-5p, miR-25-3p, miR- 29b-3p, miR-125b-5p, miR-148a-3p, miR-214-3p, miR-221-3p, miR-222-3p, and miR-421), as well as on the expression of the apoptosis-related genes BAX, BCL2, TP53, and CDKN1B in BT-20 and SKBR- 3 breast adenocarcinoma cells.
Treatment of BT-20 cells with vincristine, vinblastine, and/or vinorelbine resulted in upregulation of TP53 expression. However, no alterations in the mRNA levels of the pivotal BCL2 family members BAX and BCL2 were observed. On the other hand, treatment of SK-BR-3 cells with any of these vinca alkaloids led to an increase in the BAX/BCL2 mRNA ratio, implying the activation of the intrinsic apoptotic pathway. No concomitant alteration in TP53 expression was observed in treated SKBR- 3 cells. Regarding the miRNAs examined in this study, miR-222-3p expression exhibited the most remarkable modulations in both treated cell lines.
This study suggests the possible involvement of miR-222-3p expression in breast cancer cell apoptosis, triggered by vincristine, vinblastine, and vinorelbine.
使用天然化疗药物治疗癌症会诱导细胞凋亡，并显著改变与细胞凋亡相关的基因表达。miRNA（微小 RNA）表达失调与多种人类恶性肿瘤有关。长春花生物碱属于抗有丝分裂药物，可阻止癌细胞分裂，导致细胞凋亡。它们常用于乳腺癌的临床治疗。
本研究重点探讨长春花生物碱（长春新碱、长春碱和长春瑞滨）对乳腺癌细胞 miRNA 表达的影响。
我们研究了长春新碱、长春碱和长春瑞滨对致癌和肿瘤抑制 miRNA（miR-15a-5p、miR-16-5p、miR-21-5p、miR-25-3p、miR-29b-3p、miR-125b-5p、miR-148a-3p、miR-214-3p、miR-221-3p、miR-222-3p 和 miR-421）以及凋亡相关基因 BAX、BCL2、TP53 和 CDKN1B 在 BT-20 和 SKBR-3 乳腺癌腺癌细胞中的表达的影响。
BT-20 细胞用长春新碱、长春碱和/或长春瑞滨处理后，TP53 表达上调。然而，BCL2 家族关键成员 BAX 和 BCL2 的 mRNA 水平没有变化。另一方面，用这些长春花生物碱中的任何一种处理 SK-BR-3 细胞，都会导致 BAX/BCL2 mRNA 比值增加，提示内在凋亡途径的激活。在处理的 SKBR-3 细胞中未观察到 TP53 表达的伴随变化。在本研究中检查的 miRNA 中，miR-222-3p 在两种处理细胞系中的表达变化最为显著。
本研究表明，miR-222-3p 的表达可能参与了长春新碱、长春碱和长春瑞滨诱导的乳腺癌细胞凋亡。
