Transcriptomic and Functional Pathway Analysis of Human Cervical Carcinoma Cancer Cells Response to Microtubule Inhibitor

Abstract

BACKGROUND: There clearly is a need for effective chemotherapy for early-stage, high-risk patients with human cervical carcinoma. Vinblastine (VBL) is a key microtubule inhibitor, but unproven in its mechanisms as an important antitumor agent in cervical carcinoma. METHODS: We selected the concentration of vinblastine inducing 30% cell death for analyses assessing the DNA content, gene expression and transcriptional gene regulation of VBL-treated KB-3 cells. RESULTS: Transcriptomic and hierarchical clustering analysis demonstrated that treatment of KB-3 cells with VBL altered the expression of a diverse group of genes with G2/M arrest, which regulated by four oncogenic or tumor suppresser transcription factors (AP1, NFKB1, RELA, and TP53). Functional pathway analysis revealed the disease response to the biological effects of vinblastine in cervical carcinoma chemotherapy including protein ubiquitination pathway, RhoGDI signaling, integrin signaling, agranulocyte adhesion and biapedesis, and actin nucleation pathways. Northern blots also confirmed that KRT-7, FN14, IER3, and ID1 were deregulated in VBL-treated KB-3 cells. CONCLUSION: Transcriptional time series profiles and a functional pathway analysis of VBL-treated KB-3 cells will provide a new strategy for improving microtubule inhibitor chemotherapy for cervical carcinoma.