[Elevated expression level of wild-type survivin in gastric cancer promotes in vitro docetaxel-resistance].
OBJECTIVE
To study the expression of three survivin splicing variants in gastric cancer and to evaluate the significant correlation between survivin variants' expression and chemoresistance in gastric cancer.


METHODS
Real time quantitative RT-PCR was used to analyze the mRNA expression of survivin variants in 39 gastric tumor specimens resected during operation. The clinical resistance to anticancer agents [CDDP, MMC, 5-Fu, docetaxel (Taxotere TXT), and GEM] was analyzed by histoculture drug-response assay (HDRA).


RESULTS
Among the 39 tumor samples, survivin expression was detected in all tumor samples (39/39); 79.5% (31/39) of the samples demonstrated survivin-2B expression and 66.7% (26/39) of the samples had survivin-Delta Ex3 expression. HDRA showed that the in vitro efficacy rates of CDDP, MMC, 5Fu, TXT, and GEM were 36.8% (14/38), 31.2% (10/32), 23.1% (9/39), 20.5% (8/39), and 12.5% (4/32) respectively, equivalent to the previous HDRA studies and historical clinical studies in gastric cancer patients. The expression rate of wild-type survivin was significantly higher in the group of chemoresistance to TXT than in the group sensitive to docetaxel (P = 0.021).


CONCLUSIONS
Elevated expression level of wild-type survivin promotes docetaxel-resistance in patients with gastric cancer.
Meng
Hua
H
Department of General Surgery, Second Affiliated Hospital of Zhejiang University School of Medicine, Hangzhou 310009, China.
Lu
Cai-de
CD
Dai
De-jian
DJ
Sun
Yu-lei
YL
Tanigawa
Nobuhico
N
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D014408:Biomarkers, Tumor / Q000032:analysis; D002945:Cisplatin / Q000008:administration & dosage; D000077143:Docetaxel; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000008:administration & dosage; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins; D008297:Male; D008869:Microtubule-Associated Proteins / Q000096:biosynthesis* / Q000235:genetics; D008875:Middle Aged; D016685:Mitomycin / Q000008:administration & dosage; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis / Q000235:genetics; D013274:Stomach Neoplasms / Q000188:drug therapy / Q000378:metabolism* / Q000473:pathology; D000077022:Survivin; D043823:Taxoids / Q000008:administration & dosage / Q000494:pharmacology*
C107489:BIRC5 protein, human; D014408:Biomarkers, Tumor; D051034:Inhibitor of Apoptosis Proteins; D008869:Microtubule-Associated Proteins; D009363:Neoplasm Proteins; D012333:RNA, Messenger; D000077022:Survivin; D043823:Taxoids; D000077143:Docetaxel; D016685:Mitomycin; D002945:Cisplatin; D005472:Fluorouracil