Suppression of PI3K by Weight Loss via Dietary Calorie Restriction and/or Treadmill Exercise in TPA‐induced Mouse Skin

Abstract

Obesity or overweight by excessive calorie intake and/or sedentary lifestyle has been associated with increased cancer risks. Our previous study demonstrated that the inhibition of IGF-1 signaling such as PI3K pathway might account for the mechanisms of cancer prevention by weight control in a skin cancer mouse model. This study was designed to further investigate PI3K expression by using immunohistochemical analysis in response to weight loss by decreasing calorie intake or increasing physical activity in TPA-promoted mouse skin samples. SENCAR mice were randomly divided into three groups: ad-libitum-fed sedentary control (control), exercise with pair-feeding at a same amount as control (Ex+PF), and 20% dietary calorie restriction (DCR). After 10 weeks, body weight and percent fat composition were significantly decreased in the groups of Ex+PF and DCR when compared with the control. Western blotting showed PI3K protein levels in TPA-induced skin samples were decreased significantly in both Ex+PF and DCR groups. The distribution of PI3K protein in epidermis as measured by immunohistochemistry demonstrated a significant decrease in DCR-fed mice but not Ex+PF mice. These results present more evidence that PI3K is an important target of weight loss for potential cancer prevention (supported by NIH R01CA106397).