The overall five-year survival rate for patients with
esophageal cancer is low (15 to 25%) because of the poor prognosis at earlier stages.
Rutaecarpine (RTP) is a bioalkaloid found in the traditional Chinese herb Evodia rutaecarpa and has been shown to exhibit anti-proliferative effect on
tumor cells. However, the mechanisms by which RTP confer these effects and its importance in
esophageal squamous cell carcinoma treatment remain unclear. Thus, in the present study, we first incubated human
esophageal squamous cell carcinoma cell line, CE81T/VGH, with RTP to evaluate RTP's effects on
tumor cell growth and apoptosis. We also performed a xenograft study to confirm the in vitro findings. Furthermore, we determined the expression of p53, Bax, bcl-2,
caspase-3,
caspase-9, and
PCNA in CE81T/VGH cells or the
tumor tissues to investigate the possible mechanisms. All the effects of TRP were compared with that of
cisplatin. The results showed that RTP significantly inhibits CE81T/VGH cell growth, promotes arrest of cells in the G2/M phase, and induces apoptosis. Consistently, the in vivo study showed that
tumor size,
tumor weight, and
proliferating cell nuclear antigen protein expression in
tumor tissue are significantly reduced in the high-dose RTP treatment group. Furthermore, the in vitro and in vivo studies showed that RTP increases the expression of p53 and Bax
proteins, while inhibiting the expression of Bcl-2 in
cancer cells. In addition, RTP significantly increases the expression of cleaved
caspase-9 and cleaved
caspase-3 proteins in
tumor tissues in mice. These results suggest that RTP may trigger the apoptosis and inhibit growth in CE81T/VGH cells by the mechanisms associated with the regulation of the expression of p53, Bax, Bcl-2, as well as
caspase-9 and
caspase-3.