S-1 plus nab-paclitaxel is a promising regimen for pancreatic cancer in a preclinical model

Objectives The aim of this study was to investigate the efficacy and mechanism of action of combined S-1 and nab-paclitaxel in pancreatic cancer. Methods Three human pancreatic cancer cell lines were treated with S-1, nab-paclitaxel, alone or in combination. Mice bearing subcutaneous xenograft of the cell line, PANC-1, were treated with the same drugs. Results The growth-inhibitory effect of combined S-1 and nab-paclitaxel was greater than that of the individual drugs, and the combination index value indicated that S-1 and nab-paclitaxel had a synergistic effect in vitro. The combination of S-1 and nab-paclitaxel showed greater efficacy in vivo than monotherapy, and the growth-inhibitory effect was significantly greater when compared with the controls (P = 0.009), although no significant reduction in body weight was observed. Fractional tumor volume analysis indicated that the combination had a synergistic effect. Tumor stroma staining with α-smooth muscle actin was significantly decreased by nab-paclitaxel (P < 0.001) while the number of CD31-stained microvessel lumina was significantly increased by the combination therapy when compared with the control (P = 0.046). Conclusions S-1 and nab-paclitaxel had a synergetic effect in preclinical studies with good tolerability, and may play a role in stromal depletion and tumor angiogenesis.