Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer.
Our previous studies indicated that cyclooxygenase-2 inhibitor or octreotide could suppress the proliferation of gastric adenocarcinoma in vitro or in vivo. The present study was aimed to find whether rofecoxib combined with octreotide could enhance the inhibitive effects on the growth of gastric cancer. The effect of rofecoxib or octreotide on proliferation of gastric cancer cell line was determined by 3H-thymidine ribotide incorporation. The TdT-mediated dUTP nick end-labeling assay was used to detect the apopotosis. To determine their synergic antineoplastic effects, the interaction between rofecoxib and octreotide on SGC-7901 cell was evaluated by the median effect plot. After orthotopical implantion of xenografts of human gastric cancer in stomach, nude mice were given rofecoxib plus octreotide for 8 weeks. Cyclooxygenase-2 in gastric cancer tissues was measured by immunohistochemistry. Combination of rofecoxib and octreotide presented synergistic effect (combination index < 1) in the majority of responses. The inhibitory rate for xenografts in nude mice was 89.7% in rofecoxib group. Combination of rofecoxib and octreotide enhanced inhibitory rate to 98.8%. The combination greatly increased the apoptotic index (78.20% +/- 6.45%) of the xenografts as compared with that of using rofecoxib alone (46.60% +/- 3.42%); the difference was very significant (p < 0.001). Rofecoxib could inhibit the activity of cyclooxygenase-2 in the tissue of gastric adenocarcinomas of nude mice. Our results indicate that combination of rofecoxib and octreotide significantly enhances the antiproliferative effect in gastric adenocarcinoma, which might have potential therapeutic value.
Tang
Chengwei
C
Department of Gastroenterology, Division of Peptides Related With Human Diseases, Key Laboratory of Biotherapy of Human Diseases, Ministry of Education, West China Hospital, Sichuan University, Chengdu, China. cwtang@medmail.com.cn
Liu
Chunlun
C
Zhou
Xuchun
X
Wang
Chunhui
C
D000230:Adenocarcinoma / Q000201:enzymology / Q000473:pathology*; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D000971:Antineoplastic Combined Chemotherapy Protocols / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects*; D051546:Cyclooxygenase 2; D004347:Drug Interactions; D004357:Drug Synergism; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism; D007783:Lactones / Q000008:administration & dosage; D008297:Male; D008565:Membrane Proteins; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D015282:Octreotide / Q000008:administration & dosage; D011451:Prostaglandin-Endoperoxide Synthases / Q000378:metabolism; D013274:Stomach Neoplasms / Q000201:enzymology / Q000473:pathology*; D013450:Sulfones; D013936:Thymidine / Q000378:metabolism; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured / Q000637:transplantation
D018931:Antineoplastic Agents, Hormonal; D007527:Isoenzymes; D007783:Lactones; D008565:Membrane Proteins; D013450:Sulfones; C116926:rofecoxib; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; D011451:Prostaglandin-Endoperoxide Synthases; D015282:Octreotide; D013936:Thymidine