PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance

Background: Acquired resistance of chemotherapy, especially cisplatin, is a major challenge in lung cancer treatment. We conducted this study to examine whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse cisplatin resistance in human lung cancer cells. In addition, we explor...

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Autores principales: Liu, Minghui, Cui, Liyuan, Li, Xin, Xia, Chunqiu, Li, Yongwen, Wang, Rui, Ren, Fan, Liu, Hongyu, Chen, Jun
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley & Sons Australia, Ltd 2021
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952807/
https://www.ncbi.nlm.nih.gov/pubmed/33534964
http://dx.doi.org/10.1111/1759-7714.13866
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author Liu, Minghui
Cui, Liyuan
Li, Xin
Xia, Chunqiu
Li, Yongwen
Wang, Rui
Ren, Fan
Liu, Hongyu
Chen, Jun
author_facet Liu, Minghui
Cui, Liyuan
Li, Xin
Xia, Chunqiu
Li, Yongwen
Wang, Rui
Ren, Fan
Liu, Hongyu
Chen, Jun
author_sort Liu, Minghui
collection PubMed
description Background: Acquired resistance of chemotherapy, especially cisplatin, is a major challenge in lung cancer treatment. We conducted this study to examine whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse cisplatin resistance in human lung cancer cells. In addition, we explored the underlying mechanisms. Method: We used CCK‐8 assay to got the IC50 of PD‐0332991 and cisplatin in A549 and A549/CDDP respectively. CCK‐8 assay, CalcuSyn 2.0 software, cell cycle distribution and apoptosis used to identify PD‐0332991 could reverse the acquired resistance of cisplatin. At last, western‐blot used to show the mechanism of PD‐0332991 enhances the effects of cisplatin. Results: We found that PD‐0332991 potentiated cisplatin‐induced growth inhibition in both cisplatin‐sensitive (A549) and cisplatin‐resistant (A549/CDDP) cells via downregulation of the proliferation, induction of apoptosis (A549 increased to 7.06%; A549/CDDP increased to 7.03%), and G0/G1 cell cycle arrest (A549 increased to 9.15%; A549/CDDP increased to 49.92%). Western blot analysis revealed that PD‐0332991 enhance the effect of cisplatin through inhibit Rb‐E2Fs pathway. Conclusions: These findings suggest that PD‐0332991 could reverse the acquired resistance of cisplatin in lung cancer cells and provide a novel treatment strategy for lung cancer patients with cisplatin resistance.
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spelling pubmed-79528072021-03-17 PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance Liu, Minghui Cui, Liyuan Li, Xin Xia, Chunqiu Li, Yongwen Wang, Rui Ren, Fan Liu, Hongyu Chen, Jun Thorac Cancer Original Articles Background: Acquired resistance of chemotherapy, especially cisplatin, is a major challenge in lung cancer treatment. We conducted this study to examine whether a cyclin D kinase 4/6 (CDK4/6) inhibitor, PD 0332991, could reverse cisplatin resistance in human lung cancer cells. In addition, we explored the underlying mechanisms. Method: We used CCK‐8 assay to got the IC50 of PD‐0332991 and cisplatin in A549 and A549/CDDP respectively. CCK‐8 assay, CalcuSyn 2.0 software, cell cycle distribution and apoptosis used to identify PD‐0332991 could reverse the acquired resistance of cisplatin. At last, western‐blot used to show the mechanism of PD‐0332991 enhances the effects of cisplatin. Results: We found that PD‐0332991 potentiated cisplatin‐induced growth inhibition in both cisplatin‐sensitive (A549) and cisplatin‐resistant (A549/CDDP) cells via downregulation of the proliferation, induction of apoptosis (A549 increased to 7.06%; A549/CDDP increased to 7.03%), and G0/G1 cell cycle arrest (A549 increased to 9.15%; A549/CDDP increased to 49.92%). Western blot analysis revealed that PD‐0332991 enhance the effect of cisplatin through inhibit Rb‐E2Fs pathway. Conclusions: These findings suggest that PD‐0332991 could reverse the acquired resistance of cisplatin in lung cancer cells and provide a novel treatment strategy for lung cancer patients with cisplatin resistance. John Wiley & Sons Australia, Ltd 2021-02-03 2021-03 /pmc/articles/PMC7952807/ /pubmed/33534964 http://dx.doi.org/10.1111/1759-7714.13866 Text en © 2021 The Authors. Thoracic Cancer published by China Lung Oncology Group and John Wiley & Sons Australia, Ltd. This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Liu, Minghui
Cui, Liyuan
Li, Xin
Xia, Chunqiu
Li, Yongwen
Wang, Rui
Ren, Fan
Liu, Hongyu
Chen, Jun
PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title_full PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title_fullStr PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title_full_unstemmed PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title_short PD‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
title_sort pd‐0332991 combined with cisplatin inhibits nonsmall cell lung cancer and reversal of cisplatin resistance
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7952807/
https://www.ncbi.nlm.nih.gov/pubmed/33534964
http://dx.doi.org/10.1111/1759-7714.13866
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