This study investigated the effects of a
phytoestrogen-containing standardized soy extract (SSE) on the growth of
nonsmall cell lung cancer (NSCLC; A549) xenografts in female athymic mice.
Tumor-bearing mice received either sterile water or SSE [50 or 100 mg/(kg x d), per os], 5 d/wk, until the mean
tumor weight in each group was at least 900 mg. Treatment with SSE reduced
tumor growth in the high-dose group compared with control (P < 0.01);
tumors in both treated groups had reduced proliferation and greater apoptosis compared with controls (P < 0.05). SSE treatment also induced diffuse central
necrosis, reducing the viable tissue mass within the
tumor. Whereas
tumor levels of
epidermal growth factor receptor were comparable in control and treated mice, the expression of phosphorylated
protein kinase B (p-Akt) was lower in
tumors of mice treated with 100 mg SSE/(kg x d) than in controls (P < 0.01). The
protein level of phosphorylated
mitogen-activated protein kinase also tended to be lower (P = 0.07) in this group than in controls.
Estrogen receptor (ER)alpha and
ERbeta were present in
tumors, but their expression levels did not differ among groups. Serum
insulin-like growth factor-1 concentrations also were not affected by the treatments. In conclusion, we found that soy
phytochemicals slow the in vivo growth of NSCLC xenografts; the modulation of the Akt-signaling pathway observed in
tumors of SSE-treated mice may have a role in the activity observed. Our research provides further support for the concept that consumption of
phytoestrogens may be effective in delaying
lung cancer progression.