Mobile website
Basic Research
The role of miR-135a in regulating multi-drug resistance of small cell lung cancer
- Article
- Figures
- Metrics
- Preview PDF
- Reference
- Related
- Cited by
- Materials
Abstract:
Objective: To investigate the role of miR-135a in regulating multi-drug resistance of small cell lung cancer. Methods: The expression of miR-135a was assessed by qRT-PCR in peripheral blood samples collected from 48 patients with SCLC admitted to our department between Janurary 2008 and December 2013, which include both chemotherapy responders (28 patients) and non-responders (20 patients). The relationships between miR-135a expression and treatment response, clinical pathological features, and prognosis of patients were analyzed. We also determined the expression of miR-135a in the drug-sensitive SCLC H69 cells and drug-resistant H69AR cell line by qRT-PCR and examined the effects of miR-135a mimics and inhibitor on the sensitivities of H69 and H69AR to chemotherapy drugs ADM, DDP, VP-16 by CCK-8 assay. Results: The level of miR-135a was significantly increased in SCLC non-responders compared with that in the responders \[(2.174±3.981） vs （-1.963±3.750）， P <0.001\]. While it is not correlated with gender and age of the patients ( P >0.05), miR-135a level is statistically correlated with clinical stage, chemosensitivity and overall survival (all P <0.05). The expression of miR-135a was also markedly increased in H69AR cells compared with that in the H69 cells \[(7.841±0.392) vs (1.047±0.081)， P <0.01\]. The drug-sensitivities H69 cells became more resistant to chemotherapeutics DDP, ADM and VP-16 after transfected with miR-135a mimics, and exhibited significantly increased IC 50 \[(18.58±1.37) vs (159.27±3.29)，（24.37±2.63） vs （129.19±2.64），and（48.55±2.59） vs （359.87±2.92）μg/ml，all P <0.01\]. Furthermore, the drug-resistant H69AR cells became more sensitive to these drugs when miR135a was downregulated, and had markedly decreased IC 50 \[(247.09±11.55) vs (76.64±10.00)，（150.83±8.03） vs （40.72±5.06），（436.63±61.19） vs （163.35±20.00）μg/ml；all P <0.01\]. Conclusion: In small cell lung cancer, miR-135a participates in the regulation of the sensitivities to multi-chemotheraputic drugs, and downregulation of miR-135a may reverses the multidrug resistance.
Keywords:
Project Supported:
Project supported by the Medical Research Foundation of Guangdong Province（No. B2014310）
Clc Number:
