[Antitumor effects of chemotherapeutic drugs on fresh human gastric cancer cells and their relationships to expressions of P-glycoprotein and glutathione S transferase-pi].
OBJECTIVE
Drug-resistance is a major factor of influencing treatment efficacy of advanced gastric cancer. This study was to evaluate in vitro antitumor effects of different chemotherapeutic drugs on fresh human gastric cancer cells, and explore their relationships with expressions of P-glycoprotein (P-gp), and glutathione S transferase -pi (GST-pi) in human gastric cancer tissue.


METHODS
A total of 39 specimens of highly purified gastric cancer cells were separately exposed to 5-fluorouracil (5-FU), cisplatin (DDP), mitomycin C (MMC), adriamycin (ADM), and hydroxycamptothecin (HCPT). Inhibitory rate of cells was detected by MTT assay. Metabolic activity of cells was detected by trypan blue exclusive assay. Cell apoptosis was detected by in situ terminal deoxynucleotidyl transferase assay (TdT assay). Expressions of GST-pi and P-gp in gastric cancer tissues were detected by immunohistochemistry.


RESULTS
After exposure to antitumor drugs, morphologic changes, decrease of metabolic activity, and apoptosis were appeared in gastric cancer cells. Inhibitory rates of cancer cells exposed to MMC, DDP, 5-FU were significantly higher than those of cells exposed to ADM, and HCPT [(38.6+/-7.7)%, (38.1+/-8.8)%, and (37.8+/-10.3)% vs. (31.9+/-10.4)%, and (29.7+/-10.2)%, P < 0.01]. Apoptosis rate of cancer cells exposed to CDDP, 5-FU, and MMC were significantly higher than those of cells exposed to HCPT, and ADM [(32.1+/-7.7)%, (31.1+/-8.8)%, and (29.8+/-6.3)% vs. (21.9+/-7.4)%, and (19.9+/- 7.4)%, P < 0.05]. Positive rate of GST-pi was 66.7%(26/39), that of P-gp was 59.0%(23/39). GST-pi positive cells showed resistance to DDP and MMC, P-gp positive cells showed resistance to ADM and HCPT.


CONCLUSIONS
Overexpressions of P-gp and GST-pi might contribute to drug-resistance of tumor. Detection of GST-pi and P-gp, together with MTT chemosensitivity test, might be useful for selecting more effective chemotherapeutic drugs.
Zhang
Jun
J
Department of Surgery, Shanghai Institute of Digestive Surgery, Ruijin Hospital, Shanghai Second Medical University, Shanghai, 200025, P. R. China.
Ji
Jun
J
Ji
Yu-Bao
YB
Yuan
Fei
F
Liu
Bing-Ya
BY
Zhu
Zheng-Gang
ZG
Lin
Yan-Zhen
YZ
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000378:metabolism*; D000970:Antineoplastic Agents / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D002166:Camptothecin / Q000031:analogs & derivatives / Q000494:pharmacology; D002467:Cell Nucleus / Q000378:metabolism; D002945:Cisplatin / Q000494:pharmacology; D003593:Cytoplasm / Q000378:metabolism; D004317:Doxorubicin / Q000494:pharmacology; D019008:Drug Resistance, Neoplasm; D005260:Female; D005472:Fluorouracil / Q000494:pharmacology; D051549:Glutathione S-Transferase pi / Q000378:metabolism*; D006801:Humans; D008297:Male; D008875:Middle Aged; D016685:Mitomycin / Q000494:pharmacology; D013274:Stomach Neoplasms / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000970:Antineoplastic Agents; D016685:Mitomycin; D004317:Doxorubicin; C028098:10-hydroxycamptothecin; D051549:Glutathione S-Transferase pi; D002945:Cisplatin; D005472:Fluorouracil; D002166:Camptothecin