Search

Purpose: Co-delivery of drugs to achieve the synergistic anticancer effect is a promising strategy for lung cancer therapy. The purpose of this research is to develop a doxorubicin (DOX) and β-elemene (ELE) co-loaded, pH-sensitive nanostructured lipid carriers (DOX/ELE Hyd NLCs). Methods: In this study, DOX/ELE Hyd NLCs were produced by a hot homogenization and ultrasonication method and used for lung cancer treatment. In vitro and in vivo efficiency as well as toxicity of the system was evaluated on lung cancer cell lines and lung tumor-bearing mice. Results: DOX/ELE Hyd NLCs had a particle size of 190 nm, with a PDI lower than 0.2. DOX/ELE Hyd NLCs exhibited a significantly enhanced cytotoxicity (drug concentration causing 50% inhibition was 7.86 μg/mL), synergy antitumor effect (combination index lower than 1), and profound tumor inhibition ability (tumor inhibition ratio of 82.9%) compared with the non pH-responsive NLCs and single-drug-loaded NLCs. Conclusion: Since the synergistic effect of the drugs was found in this system, it would have great potential to inhibit lung tumor cells and tumor growth.

Yong Liu,1,* Chuanping Yang,2,* Chengsong Cao,1 Qing Li,1 Xin Jin,1 Hanping Shi3– 5 1Department of Oncology, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People’s Republic of China; 2Department of Thoracic Surgery, Xuzhou Central Hospital, Xuzhou School of Clinical Medicine, Nanjing Medical University, Xuzhou 221000, People’s Republic of China; 3Department of Gastrointestinal Surgery/Department of Clinical Nutrition, Beijing Shijitan Hospital, Capital Medical University, Beijing 100038, People’s Republic of China; 4Department of Oncology, Capital Medical University, Beijing 100069, People’s Republic of China; 5Beijing International Science and Technology Cooperation Base of Tumor Metabolism and Nutrition, Beijing 100038, People’s Republic of China*These authors contributed equally to this workCorrespondence: Hanping Shi Fax +86-0951-6743244Email shihanpingbj@126.comPurpose: Circular RNA (circRNA) is involved in the development of various cancers. However, whether circRNA can inhibit the tumorigenesis of non-small cell lung cancer (NSCLC) is still unclear. We aimed to explore the epigenetic function of tumor-suppressive circRNA (hsa_circ_RNA_0011780) and its downstream regulatory factors in NSCLC.Patients and Methods: Quantitative polymerase chain reaction (qPCR) was used to evaluate hsa_circ_11780 expression in NSCLC tissues and cell lines. The impact of high hsa_circ_11780 expression on overall survival in patients with NSCLC was tested using the Log rank test. The association between decreased hsa_circ_11780 expression and clinicopathological features in patients with NSCLC was analyzed using the Chi-squared test. In vitro cell proliferation and apoptosis were assayed using the cell counting kit-8 (CCK-8) and flow cytometry, respectively. Mice xenograft models were used to determine the tumor promoting effects of hsa_circ_11780 on NSCLC in vivo. The underlying regulatory mechanism was predicted by bioinformatics and verified by a dual-luciferase reporter assay, RNA transfection, qPCR, and Western blotting. The correlation between miR-544a and hsa_circ_11780 expression was verified using Spearman correlation coefficient.Results: The expression of hsa_circ_11780 in NSCLC tissues and cell lines strongly declined. Low hsa_circ_11780 expression is more likely to present in patients with a large tumor size (> 3cm), distant metastasis, and poor overall survival. hsa_circ_11780 overexpression strongly inhibited proliferation, migration, and invasion of NSCLC cells (H226 and A549) in vitro and inhibited tumor growth in vivo. Furthermore, hsa_circ_11780 repressed miR-544a function by competitively binding to the complementary sites of miR-544a. miR-544a released by the declining expression of hsa_circ_11780 reduced the protein concentration of F-Box and WD repeat domain containing 7 (FBXW7) in NSCLC cells.Conclusion: FBXW7 expression mediated by the hsa_circ_11780/miR-544a axis is markedly associated with the proliferation, migration, and invasion of NSCLC, resulting in decreased survival. These findings suggest that this regulatory axis may serve as a novel therapeutic target in NSCLC.Keywords: non-small cell lung cancer, hsa_circ_11780, F-box and WD repeat domain containing 7, miR-544a, proliferation, metastasis