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.
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 humangastric 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.
Authors: Fabian D Mairinger; Jan Schmeller; Sabrina Borchert; Michael Wessolly; Elena Mairinger; Jens Kollmeier; Thomas Hager; Thomas Mairinger; Daniel C Christoph; Robert F H Walter; Wilfried E E Eberhardt; Till Plönes; Jeremias Wohlschlaeger; Bharat Jasani; Kurt Werner Schmid; Agnes Bankfalvi Journal: Oncotarget Date: 2018-04-27