Affiliation:
1. Shouguang Dongcheng Hospital
2. Shouguang People’ s Hospital
3. Shiyan Hospital of Traditional Chinese Medicine
Abstract
Abstract
Objective
To investigate if inhibitory effects of propofol on proliferation, invasion and migration of non-small cell lung carcinoma (NSCLC) cells was associated with the regulation of miR-199a/PAK4 axis.
Methods
Human NSCLC A549 and H1299 cells were treated with propofol of different concentrations at different time points. Quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) was performed to evaluate miR-199a expression. A549 and H1299 cells were divided into Control, Propofol, Propofol + miR-NC and Propofol + miR-199a inhibitor groups. The proliferation, apoptosis, migration, and invasion were examined by CCK-8, flow cytometry, wound healing, and Transwell, respectively. Western blotting was used to measure the protein expression of PAK4. Xenograft model was established in nude mice to observe if propofol can mediate miR-199a expression to regulate the growth of subcutaneous xenograft tumor.
Results
Propofol can effectively enhance the expression of miR-199a in NSCLC. Compared with Control group, H1299 and A549 cells in Propofol group decreased in viability, invasion and migration, and increased in apoptosis. The inhibitory effect of propofol on NSCLC growth was reversed by miR-199a. In comparison with Propofol group, Propofol + miR-199a inhibitor group was declined in miR-199a expression and increased in PAK4 protein expression. According to dual-luciferase reporter assay, PAK4 was a target gene of miR-199a. Experiment in vivo revealed propofol can inhibit the growth and reduce the weight of xenograft tumor, which can be reversed by miR-199a inhibitor.
Conclusion
Propofol can suppress PAK4 expression by inducing miR-199a up-regulation, thereby inhibiting the proliferative, invasive and migrating abilities of NSCLC.
Publisher
Research Square Platform LLC