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

Abstract

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.

Amphiphilic Polypeptides Obtained by the Post-Polymerization Modification of Poly(Glutamic Acid) and Their Evaluation as Delivery Systems for Hydrophobic Drugs

“…According to the literature, the IC 50 for free PTX is usually between 1.1 and 8.5 ng/mL (1.3–10 nM) [ 64 , 65 , 66 ]. In our case, the IC 50 values determined for PTX and PTX-LANS were 0.8 and 2.0 ng/mL, which, considering the SD values, are in good agreement with the literature data.…”

Paclitaxel: Application in Modern Oncology and Nanomedicine-Based Cancer Therapy

“…The synergistic interaction of the conventional drug gemcitabine (brand name Gemzar) and paclitaxel by modulating acetylation and polymerization of tubulin in non-small-cell lung cancer cell lines have been shown and that the combination allows gemcitabine with paclitaxel to synergistically suppress tumour growth [ 220 ].…”

Nuclear p120 catenin is a component of the perichromosomal layer and coordinates sister chromatid segregation during mitosis in lung cancer cells

“…Further, lumican is intensively involved in tubulin-controlled mitotic progression by participating in the formation of centrosomes, mitotic spindle fibers, and the midbody at different stages of mitosis and cytokinesis [ 15 ]. The microtubule’s highly dynamic structure represents the target of tubulin-binding anticancer drugs [ 18 ]. Its stabilization, resulting in cell apoptosis, is a keystone that underlies drug–drug interaction.…”

“…Its stabilization, resulting in cell apoptosis, is a keystone that underlies drug–drug interaction. For example, paclitaxel interacts with an amino-terminal region of tubulins against depolymerization even at a low concentration [ 18 , 19 ]. It has served as an anticancer drug in treating non-small cell lung cancer (NSCLC) and other cancers.…”