Qing-Ming Wu

Mechanism of Growth Inhibitory Effects of Cyclooxygenase-2 Inhibitor–NS398 on Cancer Cells

Cyclooxygenase (COX)-2 appears to play an important role in gastrointestinal carcinogenesis, and COX-2 overexpression has been demonstrated both in esophageal adenocarcinomas and lymph nodes metastasis. The aim of our study was to investigate the mechanism of growth inhibitory effect of selective inhibition of COX-2 by NS-398 on human cancer cells. The esophageal cancer cell lines (EC9706) that express COX-2 permanently and hepatocellular carcinoma cell lines (SMMC7721) while no expression of COX-2 were studied. Two kinds of cell lines were treated with various concentrations of NS-398 (selective for COX-2 inhibition) at 0.01–0.1 mM for 24 h, 48 h and 72 h. Antiproliferation effect was measured by 3H-TdR incorporation. The cell apoptosis were determined by flow cytometry (FCM) and DNA fragmentation analysis. Survivin was detected by immunocytochemical technique. The growth inhibition could be induced by NS398 in a dose- and time-dependent manner in two kinds of cell lines. FCM analysis revealed a high sub-G1 cell peak in EC9706 group. Agarose electrophroesis showed marked apoptosis ladder pattern, but no apoptosis by NS-398 in SMMC7721. The difference of apoptosis percentage in EC9706 and SMMC7721 was (45.23 ± 1.08)% and (3.05 ± 0.15)% (p < 0.001). After 24 h incubation with NS-398 at concentration of 0.1 dmM, the expression of survivin was markedly reduced in EC9706, but not in SMMC7721. We conclude that the administration of a selective inhibitor of COX-2 significantly decreases cell growth in cancer cell lines by different mechanism. NS-398 could inhibit cell proliferation in cancer cells whether or no COX-2 expression. Nevertheless, apoptosis in the cancer cells expressing COX-2 protein increase more than those lacking COX-2.

Upregulated p27kip1 can Downregulate Survivin Expression and Inhibit Telomerase Activity in Gastric Carcinoma Cells

ABSTRACT Previous study indicated that p27kip1 gene transfer can obviously inhibit the growth of some carcinoma cells. The purpose of this study was to investigate anticarcinoma mechanism of p27kip1. Gastric carcinoma cell strain SGC-7901 was transfected with recombinant adenovirus vector carrying human p27kip1 gene (Ad-p27kip1). Expression of survivin was detected using the western blot method and activity of telomerase was examined by telomeric repeat amplification protocol (TRAP) PCR-ELISA in gastric carcinoma cells. Our results suggest that upregulated p27kip1 can downregulate survivin expression and inhibit telomerase activity in gastric carcinoma cells.