Changes in survivin messenger RNA level during cisplatin treatment in gastric cancer.
Survivin is a member of the inhibitor of apoptosis protein (IAP) family. The expression of survivin has not been reported in differentiated normal tissues, but it has been observed in many cancerous tissues. Recent studies have revealed that survivin may correlate with the chemo-radio resistance of certain malignant cells. In the present study, the correlation between the occurrence of apoptosis and the level of expression of survivin messenger RNA (mRNA) was investigated in a gastric cancer cell line (MKN-45) and in patients with advanced gastric cancer during cisplatin (CDDP) treatment. In the gastric cancer cell line, the percentage of apoptotic cells (apoptotic index: AI) did not change after 48 h incubation with low-dose CDDP (1 microg/ml), whereas the AI explosively increased between 12 and 24 h treatment with high-dose CDDP (10 microg/ml). Relative levels of expression of survivin mRNA and survivin protein increased after low- and high-dose CDDP treatment. Survivin mRNA was not detected in normal gastric mucosas. Also, in 13 patients with advanced gastric cancer who underwent CDDP-based preoperative chemotherapy, survivin mRNA was detected in only 2 cases (15.4%). Survivin mRNA was observed in the resected tumor specimens of two cases. No significant correlation between survivin mRNA expression and the occurrence of apoptosis in resected tumors or between survivin mRNA expression and patient survival was observed. These findings indicate that survivin may play an important role for the chemoresistance of this cancer cell line. However, the clinical importance of survivin expression remains unclear in patients with gastric cancer.
Ikeguchi
M
M
First Department of Surgery, Faculty of Medicine, Tottori University, Yonago, Japan. masaike@grape.med.tottori-u.ac.jp
Kaibara
N
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000970:Antineoplastic Agents / Q000494:pharmacology* / Q000627:therapeutic use; D017209:Apoptosis / Q000187:drug effects; D002868:Chromosomal Proteins, Non-Histone / Q000235:genetics*; D002945:Cisplatin / Q000494:pharmacology* / Q000627:therapeutic use; D004305:Dose-Response Relationship, Drug; D005260:Female; D005753:Gastric Mucosa / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins; D008875:Middle Aged; D009363:Neoplasm Proteins; D012333:RNA, Messenger / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000235:genetics* / Q000473:pathology; D000077022:Survivin; D013997:Time Factors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; C107489:BIRC5 protein, human; D002868:Chromosomal Proteins, Non-Histone; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D002945:Cisplatin