The role of P-glycoprotein in human gastric cancer xenografts in response to chemotherapy.
BACKGROUND
To clarify the contribution of P-glycoprotein (P-GP) to drug resistance of gastric cancer, the correlation between chemosensitivity of the tumor and expression of P-GP was examined using human gastric cancer xenografts in nude mice.


METHODS
Two strains, P-GP-positive and -negative, were established using primary explants from patients who had not received chemotherapy. Their stable growth was obtained by serial passages as subcutaneous tumors in nude mice. Mitomycin C (MMC, 3.25 mg/kg), adriamycin (ADR, 6mg/kg), or cisplatin (CDDP, 6mg/kg) was administered intraperitoneally once a week for 3 weeks.


RESULTS
In the P-GP-negative strain, all three drugs significantly suppressed the tumor growth, while in the P-GP-positive strain, only MMC did so. However, the growth inhibition of MMC was apparently greater in the P-GP-negative strain than in the positive tumor. The expressions of metallothionein (MT), glutathione-S-transferase-pi (GST-pi), and p53 were not different between the strains. Bcl-2 was expressed only in the P-GP-negative strain. Induction of P-GP expression was observed in some specimens after treatment with MMC and with CDDP.


CONCLUSIONS
P-GP might affect inherent and acquired resistance against chemotherapeutic agents in gastric cancer.
Monden
N
N
The Second Department of Surgery, Shimane Medical University, Izumo, Japan.
Abe
S
S
Hishikawa
Y
Y
Yoshimura
H
H
Kinugasa
S
S
Dhar
D K
DK
Tachibana
M
M
Nagasue
N
N
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000502:physiology*; D000818:Animals; D000903:Antibiotics, Antineoplastic / Q000627:therapeutic use*; D000970:Antineoplastic Agents / Q000627:therapeutic use*; D002945:Cisplatin / Q000627:therapeutic use*; D004317:Doxorubicin / Q000627:therapeutic use*; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D016685:Mitomycin / Q000627:therapeutic use*; D009154:Mutation; D009368:Neoplasm Transplantation; D013274:Stomach Neoplasms / Q000188:drug therapy* / Q000503:physiopathology*; D014183:Transplantation, Heterologous; D016159:Tumor Suppressor Protein p53 / Q000235:genetics / Q000378:metabolism
D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D000903:Antibiotics, Antineoplastic; D000970:Antineoplastic Agents; D016159:Tumor Suppressor Protein p53; D016685:Mitomycin; D004317:Doxorubicin; D002945:Cisplatin