Superior Antitumor Activity of Nanoparticle Albumin-Bound Paclitaxel in Experimental Gastric Cancer

Changhua Zhang, Niranjan Awasthi, Margaret Schwarz, Stefan Hinz, Roderich E. Schwarz

Research output: Contribution to journalArticle

22 Citations (Scopus)

Abstract

Gastric cancer is the second common cause of cancer related death worldwide and lacks highly effective treatment for advanced disease. Nab-paclitaxel is a novel microtubule-inhibitory cytotoxic agent that has not been tested in gastric cancer as of yet. In this study, human gastric cancer cell lines AGS, NCI-N87 and SNU16 were studied. Nab-paclitaxel inhibited cell proliferation with an IC50 of 5 nM in SNU16, 23 nM in AGS and 49 nM in NCI-N87 cells after 72-hour treatment, which was lower than that of oxaliplatin (1.05 μM to 1.51 μM) and epirubicin (0.12 μM to 0.25 μM). Nab-paclitaxel treatment increased expression of the mitotic-spindle associated phospho-stathmin irrespective of the baseline total or phosphorylated stathmin level, and induced mitotic cell death as confirmed through increased expression of cleaved-PARP and caspase-3. After a two-week nab-paclitaxel, oxaliplatin or epirubicin treatment, the average in vivo local tumor growth inhibition rate was 77, 17.2 and 21.4 percent, respectively (p = 0.002). Effects of therapy on tumoral proliferative and apoptotic indices corresponded with tumor growth inhibition data, while expression of phospho-stathmin also increased in tissues. There was an increase in median animal survival after nab-paclitaxel treatment (93 days) compared to controls (31 days, p = 0.0007), oxaliplatin (40 days, p = 0.0007) or to docetaxel therapy (81 days, p = 0.0416). The strong antitumor activity of nab-paclitaxel in experimental gastric cancer supports such microtubule-inhibitory strategy for clinical application. Nab-paclitaxel benefits were observed independent from phosphorylated stathmin expression at baseline, putting into question the consideration of nab-paclitaxel use in gastric cancer based on this putative biomarker.

Original languageEnglish (US)
Article numbere58037
JournalPLoS One
Volume8
Issue number2
DOIs
StatePublished - Feb 27 2013
Externally publishedYes

Fingerprint

paclitaxel
stomach neoplasms
nanoparticles
Nanoparticles
oxaliplatin
Stomach Neoplasms
albumins
Stathmin
epirubicin
Epirubicin
docetaxel
Microtubules
growth retardation
microtubules
neoplasms
Tumors
Neoplasms
therapeutics
mitotic spindle apparatus
Spindle Apparatus

ASJC Scopus subject areas

  • Agricultural and Biological Sciences(all)
  • Biochemistry, Genetics and Molecular Biology(all)
  • Medicine(all)

Cite this

Superior Antitumor Activity of Nanoparticle Albumin-Bound Paclitaxel in Experimental Gastric Cancer. / Zhang, Changhua; Awasthi, Niranjan; Schwarz, Margaret; Hinz, Stefan; Schwarz, Roderich E.

In: PLoS One, Vol. 8, No. 2, e58037, 27.02.2013.

Research output: Contribution to journalArticle

Zhang, Changhua ; Awasthi, Niranjan ; Schwarz, Margaret ; Hinz, Stefan ; Schwarz, Roderich E. / Superior Antitumor Activity of Nanoparticle Albumin-Bound Paclitaxel in Experimental Gastric Cancer. In: PLoS One. 2013 ; Vol. 8, No. 2.
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