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Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway
BACKGROUND: Our previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibit...
Autores principales: | , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
BioMed Central
2020
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247206/ https://www.ncbi.nlm.nih.gov/pubmed/32489321 http://dx.doi.org/10.1186/s12935-020-01270-3 |
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author | Wang, Sumei Peng, Zhiwei Li, Wenjuan Long, Shunqin Xiao, Shujing Wu, Wanyin |
author_facet | Wang, Sumei Peng, Zhiwei Li, Wenjuan Long, Shunqin Xiao, Shujing Wu, Wanyin |
author_sort | Wang, Sumei |
collection | PubMed |
description | BACKGROUND: Our previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Moreover, our recent work showed that FZKA induced lung cancer cell apoptosis via STAT3/Bcl-2/Caspase-3 pathway. Thus in this study, we aim to elucidate how FZKA enhances the effect of GFTN in lung cancer from the perspective of cell apoptosis. METHODS: Cell proliferation and colony formation assay were performed to detect the cell growth inhibition. Flow cytometry and TUNEL assay were carried out to test the cell apoptosis. Mitochondrial membrane potential (MMP) assay was done to measure the alteration of MMP. Caspase-3/-9 activity assay was used to test the activity of caspase-3/-9. Western blot and qRT-PCR were done to detect the expression of STAT3 and Bcl-2 family as well as Caspase-3/-9 and Cyt-C at protein and mRNA levels, respectively. Transient transfection was performed to silence STAT3 using siSTAT3. Animal model was done to validate the molecular mechanisms in vivo and immunohistochemistry was done to detect the expression of Bax and Caspase-3. RESULTS: Firstly, our results showed that FZKA enhanced the inhibition effect of GFTN in lung cancer both in vitro and in vivo. Secondly, cell apoptosis was enhanced when treating lung cancer cells with both FZKA and GFTN, a process involving the mitochondria and the Bcl-2 family. And Bcl-2 family was involved in this process. Interestingly, STAT3 plays a critical role on mediating the above process. Last but not the least, the enhanced effect of cell apoptosis induction of GFTN by FZKA was validated in animal model. CONCLUSION: Our findings conclude that Fuzheng Kang-Ai decoction enhances the effect of GFTN-induced cell apoptosis in lung cancer through the mitochondrial pathway, providing a novel molecular mechanism by which FZKA sensitizes to GFTN by delaying drug resistance in treating lung cancer patients. |
format | Online Article Text |
id | pubmed-7247206 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | BioMed Central |
record_format | MEDLINE/PubMed |
spelling | pubmed-72472062020-06-01 Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway Wang, Sumei Peng, Zhiwei Li, Wenjuan Long, Shunqin Xiao, Shujing Wu, Wanyin Cancer Cell Int Primary Research BACKGROUND: Our previous clinical study has shown that Chinese herbal medicine (CHM) Fuzheng Kang-Ai (FZKA) decoction is effective in treating advanced lung cancer patients through prolonging the drug resistance to Gefitinib (GFTN). Our basic study found that FZKA decoction could enhance the inhibition effect of GFTN in lung cancer by inactivating PI3K/Akt pathway. Moreover, our recent work showed that FZKA induced lung cancer cell apoptosis via STAT3/Bcl-2/Caspase-3 pathway. Thus in this study, we aim to elucidate how FZKA enhances the effect of GFTN in lung cancer from the perspective of cell apoptosis. METHODS: Cell proliferation and colony formation assay were performed to detect the cell growth inhibition. Flow cytometry and TUNEL assay were carried out to test the cell apoptosis. Mitochondrial membrane potential (MMP) assay was done to measure the alteration of MMP. Caspase-3/-9 activity assay was used to test the activity of caspase-3/-9. Western blot and qRT-PCR were done to detect the expression of STAT3 and Bcl-2 family as well as Caspase-3/-9 and Cyt-C at protein and mRNA levels, respectively. Transient transfection was performed to silence STAT3 using siSTAT3. Animal model was done to validate the molecular mechanisms in vivo and immunohistochemistry was done to detect the expression of Bax and Caspase-3. RESULTS: Firstly, our results showed that FZKA enhanced the inhibition effect of GFTN in lung cancer both in vitro and in vivo. Secondly, cell apoptosis was enhanced when treating lung cancer cells with both FZKA and GFTN, a process involving the mitochondria and the Bcl-2 family. And Bcl-2 family was involved in this process. Interestingly, STAT3 plays a critical role on mediating the above process. Last but not the least, the enhanced effect of cell apoptosis induction of GFTN by FZKA was validated in animal model. CONCLUSION: Our findings conclude that Fuzheng Kang-Ai decoction enhances the effect of GFTN-induced cell apoptosis in lung cancer through the mitochondrial pathway, providing a novel molecular mechanism by which FZKA sensitizes to GFTN by delaying drug resistance in treating lung cancer patients. BioMed Central 2020-05-24 /pmc/articles/PMC7247206/ /pubmed/32489321 http://dx.doi.org/10.1186/s12935-020-01270-3 Text en © The Author(s) 2020 Open AccessThis article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/. The Creative Commons Public Domain Dedication waiver (http://creativecommons.org/publicdomain/zero/1.0/) applies to the data made available in this article, unless otherwise stated in a credit line to the data. |
spellingShingle | Primary Research Wang, Sumei Peng, Zhiwei Li, Wenjuan Long, Shunqin Xiao, Shujing Wu, Wanyin Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title | Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title_full | Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title_fullStr | Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title_full_unstemmed | Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title_short | Fuzheng Kang-Ai decoction enhances the effect of Gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
title_sort | fuzheng kang-ai decoction enhances the effect of gefitinib-induced cell apoptosis in lung cancer through mitochondrial pathway |
topic | Primary Research |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7247206/ https://www.ncbi.nlm.nih.gov/pubmed/32489321 http://dx.doi.org/10.1186/s12935-020-01270-3 |
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