In Europe,
swainsonine has been studied widely for prevention of
metastasis and
cancer therapy. In order to investigate the effects and mechanisms of
swainsonine on the human gastric
carcinoma SGC-7901 cell, we carried out in vivo and in vitro experiments.
After treatment with
swainsonine, an effective dose and IC50 value of
swainsonine for SGC-7901 cells were examined by MTT assay. Cell-cycle distribution and apoptotic rates were analyzed using FCM, and [Ca2+]i was measured using LSCM. The expression of p53, c-myc and Bcl-2 were determined using an immunocytochemical method. Simultaneously, 50 mice were divided randomly into five groups. Three groups were administrated
swainsonine at dose of 3, 6 and 12 mg/kg body wt., two control groups were administrated N.S. 20 ml/kg body wt. and
5-Fu 20 mg/kg body wt., respectively, by
intraperitoneal injection. The inhibition rate was calculated and pathological sections were observed. The growth of SGC-7901 cell is inhibited by
swainsonine in vitro, with an IC50 value at 24 h of 0.84 microg/ml, and complete inhibition concentration is 6.2 microg/ml.
After treatment with
swainsonine at the concentrations of 0.5, 1.5 and 4.5 microg/ml for 24 h, the expression of apoptosis inhibiting gene p53 and bcl-2 decreases, and the apoptotic trigger gene c-myc increases markedly (p<0.05), as well as [Ca2+]i overloading, SGC-7901 cell is induced to apoptosis in the end. It is also found that the percentages of S phase are 38.8%, 39.7% and 29.6%, respectively (20.0% in control group and 23.2% in 5-Fu group). The rates of inhibition were 13.2%, 28.9%, 27.3%, respectively, when the nude mice were administered
swainsonine (p<0.05 or 0.01). The structure of the
tumor showed
hemorrhage,
necrosis and inflammatory cell infiltration. We therefore conclude that
swainsonine could inhibit cell proliferation in vitro and the growth of human gastric
carcinoma in vivo. The mechanisms of
swainsonine-induced apoptosis may relate to [Ca2+]i overloading and the expression of apoptosis-related genes.