scholarly journals Ze-Qi-Tang Formula Induces Granulocytic Myeloid-Derived Suppressor Cell Apoptosis via STAT3/S100A9/Bcl-2/Caspase-3 Signaling to Prolong the Survival of Mice with Orthotopic Lung Cancer

2021 ◽  
Vol 2021 ◽  
pp. 1-20
Author(s):  
Zi-hang Xu ◽  
Yang-zhuangzhuang Zhu ◽  
Lin Su ◽  
Xue-yang Tang ◽  
Chao Yao ◽  
...  

Non-small-cell lung cancer (NSCLC) remains the most common malignancy with the highest morbidity and mortality worldwide. In our previous study, we found that a classic traditional Chinese medicine (TCM) formula Ze-Qi-Tang (ZQT), which has been used in the treatment of respiratory diseases for thousands of years, could directly inhibit the growth of human NSCLC cells via the p53 signaling pathway. In this study, we explored the immunomodulatory functions of ZQT. We found that ZQT significantly prolonged the survival of orthotopic lung cancer model mice by modulating the tumor microenvironment (TME). ZQT remarkably reduced the number of MDSCs (especially G-MDSCs) and inhibited their immunosuppressive activity by inducing apoptosis in these cells via the STAT3/S100A9/Bcl-2/caspase-3 signaling pathway. When G-MDSCs were depleted, the survival promotion effect of ZQT and its inhibitory effect on lung luminescence signal disappeared in tumor-bearing mice. This is the first study to illustrate the immunomodulatory effect of ZQT in NSCLC and the underlying molecular mechanism.

2015 ◽  
Vol 35 (1) ◽  
pp. 447-453 ◽  
Author(s):  
GUANGWEI ZHONG ◽  
XI CHEN ◽  
XIA FANG ◽  
DONGSHENG WANG ◽  
MINGXUAN XIE ◽  
...  

2018 ◽  
Vol 26 (7) ◽  
pp. 1235-1250 ◽  
Author(s):  
Xiang-lin Hao ◽  
Fei Han ◽  
Ning Zhang ◽  
Hong-qiang Chen ◽  
Xiao Jiang ◽  
...  

2017 ◽  
Vol 37 (4) ◽  
Author(s):  
Xiao-Jing Li ◽  
Zhi-Feng Li ◽  
Jiu-Jiang Wang ◽  
Zhao Han ◽  
Zhao Liu ◽  
...  

The present study investigated the effects of microRNA-374 (miR-374) on human squamous cell carcinoma (SCC) cell proliferation, migration, invasion, and apoptosis through P53 signaling pathway by targeting growth arrest and DNA-damage-inducible protein 45 α (Gadd45a). Skin samples were collected from patients with skin SCC and normal skin samples. Expression of miR-374, Gadd45a, P53, P73, P16, c-myc, bcl-2, Bax, caspase-3, and caspase-9 were detected using quantitative real-time polymerase chain reaction (qRT-PCR) and Western blotting. A431 and SCL-1 cells were divided into blank, negative control (NC), miR-374 mimics, miR374 inhibitors, siRNA–Gadd45a, and miR-374 inhibitors + siRNA–Gadd45a groups. Their proliferation, migration, invasion, cell cycle, and apoptosis were evaluated by 3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide (MTT) assay, scratch test, Transwell assay, and flow cytometry. SCC skin tissues exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased levels of Gadd45a, P53, c-myc, and Bcl-2 compared with the normal skin tissues. The miR-374 inhibitors group exhibited decreased expression of miR-374, P73, P16, Bax caspase-3 and caspase-9, and increased expression of Gadd45a, P53, c-myc, and Bcl-2, enhanced cell proliferation, migration, and invasion, and reduced apoptosis compared with the blank and NC groups; the miR-374 mimics group followed opposite trends. Compared with the blank and NC groups, the miR-374 inhibitors + siRNA–Gadd45a group showed decreased miR-374 level; the siRNA–Gadd45a group showed elevated levels of P73, P16, Bax, caspase-3 and caspase-9, decreased levels of Gadd45a, P53, c-myc, and Bcl-2, reduced cell proliferation, migration, and invasion, and accelerated apoptosis. miR-374 induces apoptosis and inhibits proliferation, migration, and invasion of SCC cells through P53 signaling pathway by down-regulating Gadd45a.


2021 ◽  
Vol 11 ◽  
Author(s):  
Tao Zhang ◽  
ZhiQiang Mo ◽  
Guangfeng Duan ◽  
Rijie Tang ◽  
Fujun Zhang ◽  
...  

Purpose:125I seeds were effective in the treatment of non-small cell lung cancer in previous research. However, the exact signaling pathway-mediated apoptosis mechanism is still unclear. The present study analyzed the effects and potential mechanisms of 125I seed on the growth and migration of A549 cells.Methods: Lung cancer A549 cells were irradiated with 125I seed for various times. MTT, invasion assay, and flow cytometry were used to detect the proliferation, invasion, and apoptosis of treated cells, respectively. A Nimblegen genome-wide expression profile chip was used to evaluate gene expression changes in 125I seed-treated A549 cells. Validation studies were performed using phosphorylated protein chip technology, Western blot, nude mouse tumor xenograft assay, and immunohistochemical experiments. All statistical analyses were performed using unpaired Student's t tests and Kruskal-Wallis test.Results: Irradiation with 125I seed inhibited A549 cell proliferation and invasion and induced apoptosis (primarily early apoptosis). Irradiation with 125I seed also caused the downregulation of p38MAPK, degradation of mouse double-minute 2 homolog (MDM2), and higher expression of p53, which eventually resulted in non-small cell lung cancer cell apoptosis.Conclusion:125I seed irradiation activated the p38MAPK/MDM2/p53 signaling pathway and promoted non-small cell lung cancer cell apoptosis. Future clinical studies targeting this signal may provide a new potential therapeutic approach for non-small cell lung cancer.


2020 ◽  
Vol 11 (11) ◽  
pp. 3155-3167
Author(s):  
Zhigang Liang ◽  
Yuan Zhong ◽  
Lifei Meng ◽  
Yi Chen ◽  
Yahui Liu ◽  
...  

2020 ◽  
Vol 34 (9) ◽  
pp. 11900-11912
Author(s):  
Junjun Sun ◽  
Xuan Wang ◽  
Wenfang Liu ◽  
Ping Ji ◽  
Anquan Shang ◽  
...  

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