Abstract

In vitro studies have shown that Vitamin E succinate (VES) arrests lung cancer proliferation; however, in vivo studies have not been performed. This study examined in vivo effects of VES on lung cancer. An in vitro dose-response curve of human A549 lung cancer tumors to VES was established. A549 tumors were established in the right submammary fat pads of athymic nude mice (C57/BL/6J-Hfh11nu). Seven days after injection, mice were separated into VES and control groups. VES mice (n = 12) underwent daily intraperitoneal (IP) injection of VES (150 mg/kg in 7% dimethyl sulfoxide, 93% polyethylene glycol); control mice (n = 11) were injected with vehicle only. At 27 days, harvested tumors were measured and weighed. Lungs were stained for metastases using hematoxylin-eosin. Tumor volume and weights were compared using a two-sample t test. Tumor growth curves were compared using a mixed model analysis of variance. In vitro studies demonstrated dose-dependent manner inhibition of A549 cell proliferation by VES (IC(50) 18 mug/mL). Tumor volumes and weights differed significantly between VES and control mice with volumes of 192.6 +/- 20.4 mm(3)versus 292.9 +/- 31.4 mm(3) (P = 0.01) and weights of 168.6 +/- 20.0 mg versus 255.7 +/- 37.0 mg, respectively (P = 0.05). Tumor growth differed significantly (P < 0.001). Both groups of mice showed pulmonary metastases. Lung cancer cells appear to respond to VES, albeit incompletely. Because tumor cell response is seen, lung cancer patients may derive some benefit from VES and should be considered in eventual clinical studies using this vitamin E derivative.

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