scholarly journals Synergistic Anticancer Activity of Combined Use of Caffeic Acid with Paclitaxel Enhances Apoptosis of Non-Small-Cell Lung Cancer H1299 Cells in Vivo and in Vitro

2018 ◽  
Vol 48 (4) ◽  
pp. 1433-1442 ◽  
Author(s):  
Jie Min ◽  
Hua Shen ◽  
Wang Xi ◽  
Qing Wang ◽  
Liang Yin ◽  
...  

Background/Aims: Caffeic acid (CA) is known to possess multiple biological activities including anti-cancer activities. However, the molecular mechanisms underlying these activities in non-small-cell lung cancer (NSCLC) cells are not fully understood. We attempted to clarify whether CA could enhance paclitaxel (PTX)-induced cytotoxicity in H1299 cells. Methods: First, we tested the cytotoxic effects in both H1299 cells and normal human Bease-2b cells by cell proliferation experiments. Next, we use Annexin V/propidium iodide apoptosis analysis and flow cytometric analysis to investigate apoptosis and cell cycle arrest under the treatments mentioned above. To further pinpoint changes in apoptosis, we tested the caspase-associated apoptotic pathway, which involves the activities of caspase-3 and caspase-9. Moreover, apoptosis-related proteins and MAPK pathway proteins were examined by western blot. An H1299 xenograft nude mice model was used to further evaluate the tumor-suppressing effects of CA and PTX in vivo. Results: Combination treatment with low-dose CA and PTX decreased the proliferation of NSCLC H1299 cells but not normal Beas-2b cells. Flow cytometry showed that H1299 cells were arrested in the sub-G1 phase and apoptosis was significantly increased in H1299 cells after CA treatment. Caspase-3 and caspase-9 activities were both increased after CA treatment. Furthermore, CA increased the PTX-induced activation of Bax, Bid, and downstream cleaved PARP, and phosphorylation of extracellular signal regulated kinase1/2 and c-Jun NH2-terminal protein kinase1/2. An in vivo tumor-suppression assay demonstrated that CA and PTX combined treatment exerted a more effective suppressive effect on tumor growth in H1299 xenografts without causing significant adverse effects. Conclusions: Our results indicated that CA inhibited NSCLC H1299 cell growth by inducing apoptosis and CA and PTX combined produced a synergistic anti-cancer effect in H1299 cells.

2021 ◽  
pp. 1-13
Author(s):  
Yonglu Li ◽  
Yaxuan Wang ◽  
Xin Yu ◽  
Ting Yu ◽  
Xiaodong Zheng ◽  
...  

BMC Cancer ◽  
2016 ◽  
Vol 16 (1) ◽  
Author(s):  
Mary-Clare Cathcart ◽  
Zivile Useckaite ◽  
Clive Drakeford ◽  
Vikki Semik ◽  
Joanne Lysaght ◽  
...  

2020 ◽  
Author(s):  
Zhihong Zhang ◽  
Zhenxiu Shan ◽  
Rubin Chen ◽  
Xiaorong Peng ◽  
Bin Xu ◽  
...  

AbstractNon-small cell lung cancer (NSCLC) is a leading threat to human lives with high incidence and mortality. Circular RNAs (circRNAs) were reported to play important roles in human cancers. The purpose of this study was to investigate the role of circ_0005962 and explore the underlying functional mechanisms. The expression of circ_0005962, miR-382-5p and pyruvate dehydrogenase kinase 4 (PDK4) was detected by quantitative real-time polymerase chain reaction (qRT-PCR). Cell proliferation and cell apoptosis were assessed by cell counting kit-8 (CCK-8) assay and flow cytometry assay, respectively. The protein levels of Beclin 1, light chain3 (LC3-II/LC3-I), PDK4, Cleaved Caspase 3 (C-caspase 3) and proliferating cell nuclear antigen (PCNA) were examined using western blot analysis. Glycolysis was determined according to the levels of glucose consumption and lactate production. The interaction between miR-382-5p and circ_0005962 or PDK4 was predicted by the online tool CircInteractome or starbase and verified by dual-luciferase reporter assay and RNA immunoprecipitation (RIP) assay. Xenograft model was constructed to investigate the role of circ_0005962 in vivo. circ_0005962 expressed with a high level in NSCLC tissues and cells. Circ_0005962 knockdown inhibited proliferation, autophagy, and glycolysis but promoted apoptosis in NSCLC cells. MiR-382-5p was targeted by circ_0005962, and its inhibition reversed the role of circ_0005962 knockdown. Besides, PDK4, a target of miR-382-5p, was regulated by circ_0005962 through miR-382-5p, and its overexpression abolished the effects of miR-382-5p reintroduction. Circ_0005962 knockdown suppressed tumor growth in vivo. Circ_0005962 knockdown restrained cell proliferation, autophagy, and glycolysis but stimulated apoptosis through modulating the circ_0005962/miR-382-5p/PDK4 axis. Our study broadened the insights into understanding the mechanism of NSCLC progression.


2019 ◽  
Vol 39 (8) ◽  
Author(s):  
Fei He ◽  
Yanzhong Wang ◽  
Wanru Cai ◽  
Minjing Li ◽  
Lei Dong

Abstract Purpose: Tumor cells, with drug resistance, are associated with failed treatment and poor prognosis. Our aim was to explore potential strategy to overcome the epidermal growth factor receptor (EGFR) inhibitors resistance in non-small cell lung cancer (NSCLC). Materials and methods: Flow cytometry was used to examine and sort cells. Using MTT assay, we detected the cell viability under different conditions. Using RT-qPCR and Western blot, we determined the targeted gene expression in mRNA and protein levels. The morphology of the prepared nanoparticles was pictured by transmission electron microscopy. We also performed immunohistochemistry (IHC) and immunofluorescence (IF) to detect the proteins expression. Subcutaneous cancer models in nude mice were constructed to evaluate the anti-cancer effects in vivo. Results: Here, we observed enhanced expression of integrin αvβ3 in tumor tissues from EGFR inhibitors resistant patients. Also, integrin αvβ3-positive NSCLC cells revealed significant EGFR inhibitors resistance, resulting from the activation of Galectin-3/KRAS/RalB/TBK1/NF-κB signaling pathway. Co-encapsulating integrin αvβ3 inhibitor and EGFR inhibitor further improved the drug delivery system, leading to superior anti-cancer effects and reduced systemic toxicity. Conclusion: Our results demonstrated that co-encapsulation of erlotinib and cilengitide by MPEG-PLA (Erlo+Cilen/PP) nanoparticles revealed enhanced tumor suppression along with reduced organ damages, providing an innovative approach for NSCLC treatment.


2021 ◽  
Vol 12 (7) ◽  
Author(s):  
Jianjiao Ni ◽  
Xiaofei Zhang ◽  
Juan Li ◽  
Zhiqin Zheng ◽  
Junhua Zhang ◽  
...  

AbstractBone is a frequent metastatic site of non-small cell lung cancer (NSCLC), and bone metastasis (BoM) presents significant challenges for patient survival and quality of life. Osteolytic BoM is characterised by aberrant differentiation and malfunction of osteoclasts through modulation of the TGF-β/pTHrP/RANKL signalling pathway, but its upstream regulatory mechanism is unclear. In this study, we found that lncRNA-SOX2OT was highly accumulated in exosomes derived from the peripheral blood of NSCLC patients with BoM and that patients with higher expression of exosomal lncRNA-SOX2OT had significantly shorter overall survival. Additionally, exosomal lncRNA-SOX2OT derived from NSCLC cells promoted cell invasion and migration in vitro, as well as BoM in vivo. Mechanistically, we discovered that NSCLC cell-derived exosomal lncRNA-SOX2OT modulated osteoclast differentiation and stimulated BoM by targeting the miRNA-194-5p/RAC1 signalling axis and TGF-β/pTHrP/RANKL signalling pathway in osteoclasts. In conclusion, exosomal lncRNA-SOX2OT plays a crucial role in promoting BoM and may serve as a promising prognostic biomarker and treatment target in metastatic NSCLC.


Drug Delivery ◽  
2021 ◽  
Vol 28 (1) ◽  
pp. 1510-1523
Author(s):  
Ying Wang ◽  
Mimi Guo ◽  
Dingmei Lin ◽  
Dajun Liang ◽  
Ling Zhao ◽  
...  

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