Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines
Wiwin Is Effendi,1,2 Tatsuya Nagano,1 Motoko Tachihara,1 Kanoko Umezawa,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Masahiro Katsurada,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicin...
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| Format: | Article |
| Language: | English |
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Dove Medical Press
2019-04-01
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| Series: | Cancer Management and Research |
| Subjects: | |
| Online Access: | https://www.dovepress.com/synergistic-interaction-of-gemcitabine-and-paclitaxel-by-modulating-ac-peer-reviewed-article-CMAR |
| _version_ | 1818178504750006272 |
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| author | Effendi WI Nagano T Tachihara M Umezawa K Kiriu T Dokuni R Katsurada M Yamamoto M Kobayashi K Nishimura Y |
| author_facet | Effendi WI Nagano T Tachihara M Umezawa K Kiriu T Dokuni R Katsurada M Yamamoto M Kobayashi K Nishimura Y |
| author_sort | Effendi WI |
| collection | DOAJ |
| description | Wiwin Is Effendi,1,2 Tatsuya Nagano,1 Motoko Tachihara,1 Kanoko Umezawa,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Masahiro Katsurada,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; 2Department of Pulmonology and Respiratory Medicine, Airlangga University Medical Faculty, Surabaya 60131, IndonesiaBackground: The combination of gemcitabine (GEM) and paclitaxel (PTX) was appealing for clinical exploration due to different mechanisms of action and partially non-overlapping toxicities.Purpose: The aim of this study was to elucidate a potential effect of this combination on the proliferation of two non-small cell lung cancer (NSCLC) cell lines, A549 and H520.Materials and methods: Cell lines were treated with GEM and PTX for 48 hours to evaluate the half maximal inhibitory concentration (IC50). To determine the combination index (CI), cell lines were exposed to GEM and PTX, in a constant ratio of IC50, by various combination treatments. GEM`s effect on tubulin was assessed by western blotting and immunofluorescent staining. GEM was combined with nanoparticle albumin-bound-paclitaxel (NP) in evaluating tumor growth inhibition.Results: The IC50 of GEM and PTX in A549 and H520 were 6.6 nM and 46.1 nM, and 1.35 nM and 7.59 nM, respectively. Among the sequences explored (GEM→PTX, PTX→GEM, and GEM plus PTX simultaneously [GEM+PTX]), GEM→PTX produced a mean CI <1 in both cell lines. Western blotting and immunofluorescent staining revealed the intention expressions of acetylated tubulin protein and enhancement of tubulin polymerization within GEM→PTX group. A combination order GEM→NP also worked synergistically to suppress tumor growth.Conclusion: The GEM→PTX sequence may represent a promising candidate regimen for the treatment of NSLCL.Keywords: IC50, combination index, tubulin |
| first_indexed | 2024-12-11T20:49:02Z |
| format | Article |
| id | doaj.art-6fb87ea844e14129acb0024b9891342b |
| institution | Directory Open Access Journal |
| issn | 1179-1322 |
| language | English |
| last_indexed | 2024-12-11T20:49:02Z |
| publishDate | 2019-04-01 |
| publisher | Dove Medical Press |
| record_format | Article |
| series | Cancer Management and Research |
| spelling | doaj.art-6fb87ea844e14129acb0024b9891342b2022-12-22T00:51:16ZengDove Medical PressCancer Management and Research1179-13222019-04-01Volume 113669367945411Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell linesEffendi WINagano TTachihara MUmezawa KKiriu TDokuni RKatsurada MYamamoto MKobayashi KNishimura YWiwin Is Effendi,1,2 Tatsuya Nagano,1 Motoko Tachihara,1 Kanoko Umezawa,1 Tatsunori Kiriu,1 Ryota Dokuni,1 Masahiro Katsurada,1 Masatsugu Yamamoto,1 Kazuyuki Kobayashi,1 Yoshihiro Nishimura11Division of Respiratory Medicine, Department of Internal Medicine, Kobe University Graduate School of Medicine, Kobe 650-0017, Japan; 2Department of Pulmonology and Respiratory Medicine, Airlangga University Medical Faculty, Surabaya 60131, IndonesiaBackground: The combination of gemcitabine (GEM) and paclitaxel (PTX) was appealing for clinical exploration due to different mechanisms of action and partially non-overlapping toxicities.Purpose: The aim of this study was to elucidate a potential effect of this combination on the proliferation of two non-small cell lung cancer (NSCLC) cell lines, A549 and H520.Materials and methods: Cell lines were treated with GEM and PTX for 48 hours to evaluate the half maximal inhibitory concentration (IC50). To determine the combination index (CI), cell lines were exposed to GEM and PTX, in a constant ratio of IC50, by various combination treatments. GEM`s effect on tubulin was assessed by western blotting and immunofluorescent staining. GEM was combined with nanoparticle albumin-bound-paclitaxel (NP) in evaluating tumor growth inhibition.Results: The IC50 of GEM and PTX in A549 and H520 were 6.6 nM and 46.1 nM, and 1.35 nM and 7.59 nM, respectively. Among the sequences explored (GEM→PTX, PTX→GEM, and GEM plus PTX simultaneously [GEM+PTX]), GEM→PTX produced a mean CI <1 in both cell lines. Western blotting and immunofluorescent staining revealed the intention expressions of acetylated tubulin protein and enhancement of tubulin polymerization within GEM→PTX group. A combination order GEM→NP also worked synergistically to suppress tumor growth.Conclusion: The GEM→PTX sequence may represent a promising candidate regimen for the treatment of NSLCL.Keywords: IC50, combination index, tubulinhttps://www.dovepress.com/synergistic-interaction-of-gemcitabine-and-paclitaxel-by-modulating-ac-peer-reviewed-article-CMARIC50combination indexα-tubulin |
| spellingShingle | Effendi WI Nagano T Tachihara M Umezawa K Kiriu T Dokuni R Katsurada M Yamamoto M Kobayashi K Nishimura Y Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines Cancer Management and Research IC50 combination index α-tubulin |
| title | Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines |
| title_full | Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines |
| title_fullStr | Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines |
| title_full_unstemmed | Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines |
| title_short | Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines |
| title_sort | synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non small cell lung cancer cell lines |
| topic | IC50 combination index α-tubulin |
| url | https://www.dovepress.com/synergistic-interaction-of-gemcitabine-and-paclitaxel-by-modulating-ac-peer-reviewed-article-CMAR |
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