Inhibitory effect of octreotide on gastric cancer growth<i>via</i>MAPK pathway

Wang, Chunhui; Tang, Chengwei; Liu, Chunlun; Tang, Liping

doi:10.3748/wjg.v9.i9.1904

Cited by 20 publications

(12 citation statements)

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“…6,10 The antineoplastic action of octreotide is thought to be mediated through the receptors for SST that may trigger the MAPK pathways. 11,12 Cellular proliferation is achieved through entry of cells from G 0 into the active cell cycle, whereas progression through the cell cycle is controlled by a spectrum of regulatory proteins. COX-2 or SST may modulate expression of a cascade of genes that control cell proliferation at different site of intracellular pathway.…”

mentioning

confidence: 99%

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer

Tang¹,

Liu²,

Zhou³

et al. 2004

Intl Journal of Cancer

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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 3 H-thymidine ribotide incorporation. The TdT-mediated dUTP nick endlabeling 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. © 2004 Wiley-Liss, Inc. Key words: rofecoxib; octreotide; gastric adenocarcinoma; cyclooxygenase-2The poor prognosis of unresectable gastric adenocarcinoma and the various disappointing therapeutic modalities make further investigation of new therapeutic approach for advanced gastric cancer of primary importance. Accumulative evidence has shown that overexpression of cyclooxygenase-2 (COX-2) in gastric adenocarcinoma might play a crucial role in invasive tumor growth and offer a new strategy against cancer by the use of COX-2 inhibitors. [1][2][3][4] The inhibitive effect of aspirin or rofecoxib, a higher selective COX-2 inhibitor 5 on the proliferation of gastric cancer, has been observed in our previous studies. 6,7 Various studies have demonstrated that the growth of normal cells and malignant tumor may be regulated by gut peptides. 8,9 In the stomach, besides the known inhibitory function of somatostatin (SST) on acid secretion, it has been suggested that the analogues of SST could be candidates for arresting the growth of gastric adenocarcinoma. Previous data from the literature have shown that the mean tumor volume in nude mice treated with octreotide, an analogue of SST, was significantly lower than that of control group with an inhibitory rate of 60.6%. 6,10 The antineoplastic action of octreotide is thought to be mediated through the receptors for S...

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mentioning

confidence: 99%

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer

Tang¹,

Liu²,

Zhou³

et al. 2004

Intl Journal of Cancer

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“…10 Although the anti-neoplastic mechanisms behind rofecoxib and octreotide are different, they may synergistically inhibit the AP-1 pathway, showing a close association with the signal transduction pathways of oncogene and therefore affecting the proliferation of tumor cells. 17,18 In the present study, celecoxib at low dose combined with octreotide was able to arrest the growth of SGC-7901/ ADR cells significantly as well. The combination strategy showed a greater growth inhibition of the Adriamycin-resistant cell SGC-7901/ADR than by celecoxib alone.…”

Section: Discussionmentioning

confidence: 77%

Effects of non‐cytotoxic drugs on the growth of multidrug‐resistance human gastric carcinoma cell line

Wang¹,

Zheng²,

Ou³

et al. 2009

J of Digest Diseases

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OBJECTIVE:To investigate the effects of the noncytotoxic drug (cyclooxygenase-2 (COX-2) inhibitor and octreotide) on growth of the multidrug-resistant human gastric carcinoma cell line SGC-7901/ADR. METHODS:The effects of non-cytotoxic drug on the growth of SGC-7901 and SGC-7901/ADR cells were evaluated by 3 H-thymidine incorporation assay. The apoptosis of cells was measured by the TdT-mediated dUTP nick end-labeling assay (TUNEL) and flow cytometric assay. Western blotting was used to analysis the expression of cyclooxygenase (COX-2) protein in SGC-7901 cells and SGC-7901/ADR cells and P-glycoprotein (P-gp) from SGC-7901/ADR cells with variable treatments. Activator protein-1 binding activity was examined by electrophoretic mobility shift assay. RESULTS:3 H-thymidine incorporation into SGC-7901/ADR cells treated with celecoxib was significantly lower than that of control group (471.3 ± 79.7 cpm vs 917.5 ± 130.8 cpm, P < 0.05). When combined with octreotide, celecoxib presented lower 3 H-thymidine incorporations than its used alone and decreased to 53.3% of that amount original. Either celecoxib or the combination group markedly induced apoptosis in SGC-7901/ADR cells. COX-2 protein in the SGC-7901/ ADR cells was higher than in that of the SGC-7901 cells (1.543 ± 0.052 vs 0.564 ± 0.021, P < 0.05). The inhibition of P-gp could be achieved with celecoxib alone and combination with octreotide (0.486 ± 0.012, 0.252 ± 0.014 vs 0.941 ± 0.033, P < 0.05). Moreover, AP-1 binding activity could be suppressed by noncytotoxic drug and showed a synergistic effect. CONCLUSION:The combination of non-cytotoxic drug significantly improved the inhibitive effects on the growth of multidrug-resistant human gastric cancer cells.

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“…15 So it is important for the treatment of A B C D only in most neuroendocrine neoplasms, 16 but also in those tumors that originate from the central nervous system, breast, and lung. [17][18][19] It was reported that SSTR2 expressed in gastric cancers, and SSTR2, SSTR3 mRNA expressed in gastric cancer cell line SGC7901, 20,21 which belongs to moderate-differentiated adenocarcinoma. But little is known about the expression and function of the human SSTR3 in human gastric cancer tissues.…”

Section: Discussionmentioning

confidence: 99%

The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells

Yi²,

Hao³

et al. 2004

Cancer Biology & Therapy

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ABBREVIATIONS Research PaperThe Effect of Somatostatin and SSTR3 on Proliferation and Apoptosis of Gastric Cancer Cells ABSTRACTIn the present study, we detected the expression of SSTR3 protein in 40 patients with gastric adenocarcinoma and 40 cases of normal gastric mucosa by immunoperoxidased staining. SSTR3 mRNA and protein were also examined in gastric cancer cell lines and eternal gastric epithelial cell line by RT-PCR, immunofluorescence and Western blot. The effect of octreotide on the growth of gastric cancer cells was examined by MTT test, and the apoptosis by flow cytometry. Competitive protein binding method was also used to evaluate the role of SSTR3. The results were: (1) SSTR3 protein existed in the membrane of gastric cancer cells. In normal gastric mucosa, SSTR3 protein distributed to the cellular membrane and cytoplasm or interstitial tissue in submucosa. The expression of SSTR3 protein was significantly lower in gastric cancer compared with normal mucosa. Moreover, the poor-differentiated adenocarcinoma was lower than the well-differentiated adenocarcinoma, and the similar result in cell lines. (2) Octreotide could inhibit the growth and induce the apoptosis of gastric cancer and normal epithelial cells that expressed SSTR3, but didn't affect the cells with no or weakly expression of SSTR3. (3) When the cells were administrated octreotide in combination of SSTR3 antibody, the effect of octreotide decreased dramatically. The preliminary study suggested that SSTR3 might play a role in the growth and apoptosis of gastric cancer. In those gastric cancers that expressed SSTR3, octreotide could be effective in inhibiting cell growth and inducing cell apoptosis through mediation of SSTR3.

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Inhibitory effect of octreotide on gastric cancer growthviaMAPK pathway

Abstract: Inhibition of sequential molecular events in MAPK pathway may interpret the mechanisms underlying the effect of octreotide on the growth of gastric adenocarcinoma.

Cited by 20 publications

References 35 publications

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer

Enhanced inhibitive effects of combination of rofecoxib and octreotide on the growth of human gastric cancer

Effects of non‐cytotoxic drugs on the growth of multidrug‐resistance human gastric carcinoma cell line

The effect of somatostatin and SSTR3 on proliferation and apoptosis of gastric cancer cells

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