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Survivin expression modulates the sensitivity of A549 lung cancer cells resistance to vincristine.
| Content Provider | Semantic Scholar |
|---|---|
| Author | Zhou, Chengwei Zhu, Yonggang Lu, Bin Zhao, Weijun Zhao, Xiaodong |
| Copyright Year | 2018 |
| Abstract | Lung cancer is the leading cause of cancer-associated mortalities worldwide. Chemotherapeutic drug vincristine is widely used to treat lung cancer; however, the acquisition of drug resistance is the major limitation of chemotherapy, and it is thus important to determine the mechanism underlying vincristine resistance in lung cancer. Survivin has been reported to be associated with the development of drug resistance and be involved in the progression of non-small cell lung cancer. In the present study, a vincristine-resistant lung cancer cell line, A549/VCR, was used to investigate the possible involvement of survivin in the acquisition of vincristine resistance. Western blot analysis demonstrated that survivin protein expression level was markedly higher in A549/VCR cells compared with in control A549 cells, whereas p53 expression level was lower in A549/VCR cells compared with in A549 cells. Thus, wild-type p53 was overexpressed in A549/VCR cells and it reversed vincristine resistance of A549/VCR cells via the inhibition of survivin expression. Furthermore, survivin was knocked down by small interfering RNA technology and the effects on viability and apoptosis of resistant cells were investigated. MTT, Annexin V-fluorescein isothiocyanate/propidium iodide and caspase-3 activity assays indicated that survivin silencing significantly inhibited cell viability and enhanced apoptosis induced by vincristine treatment in A549/VCR cells compared with non-silenced A549/VCR cells. These results suggested that survivin expression regulated by p53 may serve an important role in drug resistance in A549/VCR cells and may be a potential target for enhancing vincristine sensitivity in A549 lung cancer cells. Additionally, the present study revealed that A549/VCR cells exhibited cross resistance to methotrexate (MTX) and survivin silencing re-sensitized A549/VCR cells to MTX, indicating the crucial role of survivin in regulating A549 cells sensitivity to anticancer drugs. The results of the present study are significant for determining the underlying mechanism of vincristine resistance in lung cancer. |
| Starting Page | 5466 |
| Ending Page | 5472 |
| Page Count | 7 |
| File Format | PDF HTM / HTML |
| Alternate Webpage(s) | https://www.spandidos-publications.com/ol/16/4/5466/download |
| PubMed reference number | 30250619v1 |
| Alternate Webpage(s) | https://doi.org/10.3892/ol.2018.9277 |
| DOI | 10.3892/ol.2018.9277 |
| Journal | Oncology letters |
| Volume Number | 16 |
| Issue Number | 4 |
| Language | English |
| Access Restriction | Open |
| Subject Keyword | Annexins Apoptosis Cell Survival Iodides Isothiocyanates Methotrexate Mortality Vital Statistics Neoplasms Non-Small Cell Lung Carcinoma Propidium Iodide RNA Small cell carcinoma of lung Vincristine annexin A5 cancer cell caspase-3 fluorescein sodium monooxyethylene trimethylolpropane tristearate phenethyl isothiocyanate protein expression |
| Content Type | Text |
| Resource Type | Article |
