Expression of P-glycoprotein influences resistance against anthracyclines in clinical gastric carcinomas.
In 58 human gastric cancers, the expression of P-glycoprotein (P-gp) was evaluated immunohistochemically and chemosensitivity was determined using the in vitro succinate dehydrogenase inhibition (SDI) test. Tumors which contained over 75% stained cells were scored as positive, and 14 of 58 cases (24%) were positive. There was no significant correlation between P-gp expression and clinicopathologic features. The succinate dehydrogenase (SD) activity for each drug of P-gp positive and negative tumors was as follows: 81.8 +/- 15.2% vs. 66.3 +/- 16.1% for Adriamycin (ADM), 75.5 +/- 14.2% vs. 59.1 +/- 17.6% for aclacinomycin A (ACR), 71.7 +/- 15.0% vs. 61.1 +/- 14.0% for mitomycin C (MMC), and 57.5 +/- 18.4% vs. 47.0 +/- 16.7% for cisplatin (CDDP). The increase in SD activity was evident in P-gp positive tumors compared with negative ones in cases of ADM (P = 0.0044), ACR (P = 0.0105), and MMC (P = 0.0353). We suggested that P-gp expression is closely related to chemosensitivities of human gastric cancers to anthracyclines.
Orita
H
H
Department of Surgery II, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Maehara
Y
Y
Anai
H
H
Baba
H
H
Kusumoto
H
H
Korenaga
D
D
Sugimachi
K
K
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D015250:Aclarubicin / Q000494:pharmacology; D000903:Antibiotics, Antineoplastic / Q000494:pharmacology*; D002352:Carrier Proteins / Q000032:analysis*; D002945:Cisplatin / Q000494:pharmacology; D004317:Doxorubicin / Q000494:pharmacology; D004351:Drug Resistance; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis*; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000737:chemistry* / Q000473:pathology; D013385:Succinate Dehydrogenase / Q000037:antagonists & inhibitors
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D002352:Carrier Proteins; D008562:Membrane Glycoproteins; D016685:Mitomycin; D015250:Aclarubicin; D004317:Doxorubicin; D013385:Succinate Dehydrogenase; D002945:Cisplatin