title: The role of Six1 signaling in paclitaxel-dependent apoptosis in MCF-7 cell line.
abstract: The resistance of cancer cells to chemotherapeutic agents represents the main problem in cancer treatment. Despite intensive research, mechanisms of resistance have not yet been fully elucidated. Six1 signaling has an important role in the expansion of progenitor cell populations during early embryogenesis. Six1 gene overexpression has been strongly associated with aggressiveness, invasiveness, and poor prognosis of different cancers. In this study, we investigated the role of Six1 signaling in resistance of MCF-7 breast cancer cells to taxanes. We first established in vitro paclitaxel-resistant MCF-7 breast cancer cells. Morphological modifications in paclitaxel-resistant cells were examined via light microscopic images and fluorescence-activated cell sorting analysis. Applying quantitative real-time polymerase chain reaction, we measured Six1, B-cell lymphoma/leukemia(BCL-2), BAX, and P53 mRNA expression levels in both non-resistant and resistant cells. Resistant cells were developed from the parent MCF-7 cells by applying increasing concentrations of paclitaxel up to 64 nM. The inhibitory concentration 50% value in resistant cells increased from 3.5 ± 0.03 to 511 ± 10.22 nM (p = 0.015). In paclitaxel-resistant cells, there was a significant increase in Six1 and BCL-2 mRNA levels (p = 0.0007) with a marked decrease in pro-apoptotic Bax mRNA expression level (p = 0.03); however, there was no significant change in P53 expression (p = 0.025). Our results suggest that identifying cancer patients with high Six1 expression and then inhibition of Six1 signaling can improve the efficiency of chemotherapeutic agents in the induction of apoptosis.
authors.affiliation: Drug Applied Research Center and Department of Medical Biotechnology, Tabriz University of Medical Sciences. parisaarmat@yahoo.com.
authors.forename: Marzieh
authors.initials: M
authors.lastname: Armat
authors.forename: Taiebeh
authors.initials: T
authors.lastname: Oghabi Bakhshaiesh
authors.forename: Mehdi
authors.initials: M
authors.lastname: Sabzichi
authors.forename: Dariush
authors.initials: D
authors.lastname: Shanehbandi
authors.forename: Simin
authors.initials: S
authors.lastname: Sharifi
authors.forename: Ommoleila
authors.initials: O
authors.lastname: Molavi
authors.forename: Jamal
authors.initials: J
authors.lastname: Mohammadian
authors.forename: Mohammad
authors.initials: M
authors.lastname: Saeid Hejazi
authors.forename: Nasser
authors.initials: N
authors.lastname: Samadi
mesh_terms: D000970:Antineoplastic Agents / Q000494:pharmacology; D017209:Apoptosis; D001943:Breast Neoplasms / Q000188:drug therapy* / Q000473:pathology; D045744:Cell Line, Tumor; D002470:Cell Survival; D019008:Drug Resistance, Neoplasm; D005260:Female; D005434:Flow Cytometry; D015972:Gene Expression Regulation, Neoplastic; D018398:Homeodomain Proteins / Q000378:metabolism*; D006801:Humans; D061986:MCF-7 Cells; D017239:Paclitaxel / Q000494:pharmacology*; D019253:Proto-Oncogene Proteins c-bcl-2 / Q000378:metabolism; D012333:RNA, Messenger / Q000378:metabolism; D060888:Real-Time Polymerase Chain Reaction; D015398:Signal Transduction; D016159:Tumor Suppressor Protein p53 / Q000378:metabolism; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: D000970:Antineoplastic Agents; C494826:BAX protein, human; C000595707:BCL2 protein, human; D018398:Homeodomain Proteins; D019253:Proto-Oncogene Proteins c-bcl-2; D012333:RNA, Messenger; C099236:SIX1 protein, human; C495901:TP53 protein, human; D016159:Tumor Suppressor Protein p53; D051028:bcl-2-Associated X Protein; D017239:Paclitaxel