Traditional Chinese medicine Ze-Qi-Tang formula inhibit growth of non-small-cell lung cancer cells through the p53 pathway
| Autor: | Xiao Chen, Luyao Wei, Ning Zhang, Chenyuan Gong, Fei Zhang, Qin Zhou, Chunpu Zou, Chao Yao, Hairong Zhong, Yangzhuangzhuang Zhu, Zihang Xu, Xiaowen Zhu, Shiguo Zhu, Fei Liu |
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| Rok vydání: | 2019 |
| Předmět: |
Male
Lung Neoplasms Time Factors Cell cycle checkpoint Mice Nude Apoptosis Mice 03 medical and health sciences chemistry.chemical_compound 0302 clinical medicine Carcinoma Non-Small-Cell Lung Cell Line Tumor Drug Discovery medicine Animals Humans Propidium iodide Medicine Chinese Traditional Cell Proliferation 030304 developmental biology Pharmacology A549 cell 0303 health sciences Dose-Response Relationship Drug Cell growth business.industry Cell Cycle Cancer Cell Cycle Checkpoints Cell cycle medicine.disease Antineoplastic Agents Phytogenic Xenograft Model Antitumor Assays respiratory tract diseases chemistry A549 Cells 030220 oncology & carcinogenesis Cancer cell Cancer research Tumor Suppressor Protein p53 business Drugs Chinese Herbal |
| Zdroj: | Journal of Ethnopharmacology. 234:180-188 |
| ISSN: | 0378-8741 |
| DOI: | 10.1016/j.jep.2019.01.007 |
| Popis: | Ethnopharmacological relevance Ze-Qi-Tang (ZQT), a classic Chinese herbal formula, has been for over thousand years used for the treatment of several respiratory ailments like cough, asthma, hydrothorax and lung cancer. Aim of study Cumulative literature on ZQT herbal formula reveals that its several constituent components are potent inducer of apoptosis in different cancer cells. However, the activity of ZQT against non-small-cell-lung cancer (NSCLC) has not been previously examined. The aim of the study is to investigate the molecular mechanism of ZQT on NSCLC cells. Materials and methods Cell growth were determined by CCK-8 and colony formation assay. Induction of cellular apoptosis or arrest of cell cycle were determined by flow cytometric analysis using annexin V/ propidium iodide, Hoechst 33342 or TUNEL staining method. In some assay p53 activity of NSCLC ( A549 and H460) cells were blocked with pifithrin-a, prior to treatment with ZQT. The level of expression of cell cycle and apoptosis related marker proteins were estimated by western blot. The anticancer activity of ZQT in vivo were monitored in nude mice that were induced with tumor by subcutaneous inoculation of A549 cells and then treated by ZQT(100 mg/kg,200 mg/kg,400 mg/kg) gavaging for 30 days. Mice’ body weight and tumor volume were measured weekly. The survival carve was recorded. Apoptosis from mice’ tissue was observed by TUNEL assay. Pathological histology of liver, kidney and heart were detected by H&E staining, and its functions were tested by ELISA. Results Dose- and time-dependent inhibition of proliferation of NSCLC ( A549 and H460) cells by ZQT therapy along with induction of cell cycle arrest at G0⁄G1 phase were observed. The arrest of cell cycle arrest and inhibition of cellular proliferation were associated with up regulation of p53 along with down regulation of Cyclin B1 and Cdk2 indicating a mitochondrial related induction of apoptosis with ZQT. A reversal of ZQT-induced apoptosis and G0⁄G1 arrest was observed with pifithrin-a pretreatment. ZQT was also found to suppress the progression of tumor growth in mouse xenograft models and prolong survival. In addition, no hepato- or nephro- or cardio-toxicity with ZQT treatment were detected in mice. Conclusion These findings suggest that the ZQT formula inhibits the growth of NSCLC cells and is a potential agent of complementary and alternative treatment for lung cancer. |
| Databáze: | OpenAIRE |
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