ABSTRACT
Abstract Paclitaxel (PTX) is one of the most effective drugs used in the treatment of breast cancer. Nonetheless, the appearance of MDR1 (multidrug resistance 1) in tumor cells has become a significant hindrance for efficacious chemotherapy. In this study, we show that the expression level of Egr-1 (early growth response gene-1) in cancer tissues (from paclitaxel chemotherapy failure patients) and MCF-7/PTX cells (the breast cancer cell line that was resistant to paclitaxel) was increased. Cell proliferation assay and apoptosis assay revealed that Egr-1 could promote cell growth and inhibit apoptosis in MCF-7/PTX. Mechanistic studies indicated that Egr-1 could bind to the proximal MDR1 promoter and enhance MDR1 transcription. These findings indicate that paclitaxel induced Egr-1 accumulation and upregulated the expression of MDR1, thereby inducing the drug resistance in MCF-7/PTX. Our results suggest a novel pathway by which paclitaxel induces MDR1 expression, possibly illuminating a potential target pathway for the prevention of MDR1-mediated drug resistance.
Subject(s)
Breast Neoplasms/pathology , Drug Resistance , ATP Binding Cassette Transporter, Subfamily B, Member 1/analysis , Pharmaceutical Preparations/analysisABSTRACT
BACKGROUND: Aberrant expression of circular RNAs (circRNAs) is implicated in tumorigenesis and disease progression. However, the underlying molecular mechanisms and physiological functions of hsa_circ_0005075 in human colorectal cancer are still poorly understood. METHODS: Quantitative real-time PCR (qRT-PCR) was performed to detect the expression level of hsa_circ_0005075 in colorectal cancer. Correlations of hsa_circ_0005075 expression with pathological parameters and overall survival were assessed. CCK-8 and Transwell invasion assays were utilized to determine the effect of hsa_circ_0005075 on proliferation and invasion of colorectal cancer cells. RESULTS: Hsa_circ_0005075 was overexpressed in colorectal cancer tissues compared with paracancerous tissues and intestinal polyps. Its expression level was associated with distal metastasis, invasion, tumor node metastasis stage, and tumor diameter in colorectal cancer, and was negatively correlated with overall survival of patients with colorectal cancer. Moreover, enforced expression of hsa_circ_0005075 potentiated the proliferation and invasive behavior of colorectal cancer cells. CONCLUSIONS: Our findings suggested that hsa_circ_0005075 expression was increased in colorectal cancer and might serve as a promising diagnostic mark and therapy target of colorectal cancer.
Subject(s)
Colorectal Neoplasms/diagnosis , Colorectal Neoplasms/genetics , RNA, Circular/metabolism , Cell Movement , Cell Proliferation , Colorectal Neoplasms/metabolism , Female , Humans , Male , TransfectionABSTRACT
BACKGROUND: The aim of this study was to investigate the synergistic effect of paclitaxel (PTX) and verapamil (VERA) on adriamycin (ADR)-resistant breast cancer (MCF-7/ADR) cells. METHODS: ATP-PCA was applied to determine the inhibitory effects of PTX combined with VERA on MCF-7/ADR cells. Edu, CCK-8 and Flow cytometry (FCM), Annexin V-FITC binding and Western blot were used to analyze the effects of combination therapy with PTX and VERA on cell proliferation, progression of cell cycle and cell apoptosis. RESULTS: PTX-based treatments with VERA enhanced killing effect on MCF-7/ADR cells. IC50 value of cell was significantly decreased in combination treatment compared with PTX administrated. VERA enhanced the efficacy and sensitivity of PTX to MCF-7/ADR cells. Combination of PTX and VERA could inhibit cell proliferation via arresting progression of cell cycle and promote cell apoptosis. CONCLUSION: PTX, along with VERA, had a synergistic action in anti-tumor response and may be proposed as a novel treatment strategy for chemo-resistant breast cancer.