Abstract
OBJECTIVE: Hydroxycamptothecin (HCPT) is a unique antitumor drug that acts directly on topoisomerase I and inhibits its activity. However, the mechanism of HCPT‐induced apoptosis is unclear. In the present study, the mechanism of HCPT‐induced apoptosis in gastric cancer cells was investigated by detecting the expression of p53, c‐myc, bcl‐2, bcl‐xl and bcl‐xs genes in gastric cancer cells. METHODS: Apoptosis of gastric cancer cells (SGC‐7901, MKN‐45) was determined by terminal deoxyribonucleotidyl transferase‐mediated dUTP– digoxigenin nick‐end labeling (TUNEL) and flow cytometry. The mRNA and protein levels of the p53, c‐myc, bcl‐2, bcl‐xl and bcl‐xs genes were tested by reverse transcription–polymerase chain reaction analysis and immunocytochemical stain, respectively. RESULTS: Hydroxycamptothecin may induce apoptosis in different differentiated gastric cancer cells. The effect of HCPT‐induced apoptosis on gastric cancer cells was dependent on the dose of HCPT used and the time of exposure to HCPT. Both SGC‐7901 and MKN‐45 cells manifested some morphological features of apoptosis after 12 h exposure to HCPT, including cell shrinkage, nuclear condensation, DNA fragmentation and formation of apoptotic bodies. Some typical subdiploid peaks before the G0/G1 phase were observed. The apoptotic rates induced by 10 μg/mL HCPT in SGC‐7901 and MKN‐45 cells were 21.88 and 12.34%, respectively. The mRNA and protein levels of p53 and bcl‐2 were downregulated after treatment with HCPT in SGC‐7901 cells. However, the c‐myc, bcl‐xl and bcl‐xs protein levels were unchanged in SGC‐7901 cells. In MKN‐45 cells, the mRNA and protein levels of p53 increased after treatment with HCPT, whereas the protein levels of bcl‐2, c‐myc, bcl‐xl and bcl‐xs remained unchanged. CONCLUSIONS: Our results indicate that HCPT‐induced apoptosis in gastric cancer cells may be regulated through modulation of the expression of p53 and bcl‐2 genes.
Published Version
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