title: Superior antitumor activity of nanoparticle albumin-bound paclitaxel in experimental gastric cancer.
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.
authors: Division of Surgical Oncology, Department of Surgery, The University of Texas Southwestern Medical Center, Dallas, Texas, United States of America.
authors: Changhua
authors: C
authors: Zhang
authors: Niranjan
authors: N
authors: Awasthi
authors: Margaret A
authors: MA
authors: Schwarz
authors: Stefan
authors: S
authors: Hinz
authors: Roderich E
authors: RE
authors: Schwarz
mesh_terms: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins / Q000494:pharmacology / Q000627:therapeutic use; D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology / Q000627:therapeutic use*; D016923:Cell Death / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D005260:Female; D059565:G2 Phase Cell Cycle Checkpoints / Q000187:drug effects; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D008938:Mitosis / Q000187:drug effects; D053758:Nanoparticles / Q000627:therapeutic use*; D017239:Paclitaxel / Q000494:pharmacology / Q000627:therapeutic use*; D010766:Phosphorylation / Q000187:drug effects; D050777:Stathmin / Q000378:metabolism; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000473:pathology; D016019:Survival Analysis; D023041:Xenograft Model Antitumor Assays
chemical_list: D000068196:Albumin-Bound Paclitaxel; D000418:Albumins; D000970:Antineoplastic Agents; C493995:STMN1 protein, human; D050777:Stathmin; D017239:Paclitaxel