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Synergistic interaction of gemcitabine and paclitaxel by modulating acetylation and polymerization of tubulin in non-small cell lung cancer cell lines

Authors Effendi WI, Nagano T, Tachihara M, Umezawa K, Kiriu T, Dokuni R, Katsurada M, Yamamoto M, Kobayashi K, Nishimura Y

Received 7 November 2018

Accepted for publication 5 April 2019

Published 29 April 2019 Volume 2019:11 Pages 3669—3679

DOI https://doi.org/10.2147/CMAR.S193789

Checked for plagiarism Yes

Review by Single-blind

Peer reviewers approved by Dr Andrew Yee

Peer reviewer comments 2

Editor who approved publication: Dr Kenan Onel


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 Nishimura1

1Division 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, Indonesia

Background: 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

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