The inhibitory effect of pseudolaric acid B on gastric cancer and multidrug resistance via Cox-2/PKC-α/P-gp pathway.

Abstract

AIM:

To investigate the inhibitory effect of pseudolaric acid B on subcutaneous xenografts of human gastric adenocarcinoma and the underlying molecular mechanisms involved in its multidrug resistance.

METHODS:

Human gastric adenocarcinoma SGC7901 cells and drug-resistant SGC7901/ADR cells were injected into nude mice to establish a subcutaneous xenograft model. The effects of pseudolaric acid B with or without adriamycin treatment were compared by determining the tumor size and weight. Cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein expression levels were determined by immunohistochemistry and western blot.

RESULTS:

Pseudolaric acid B significantly suppressed the tumor growth induced by SGC7901 cells and SGC7901/ADR cells. The combination of pseudolaric acid B and the traditional chemotherapy drug adriamycin exhibited more potent inhibitory effects on the growth of gastric cancer in vivo than treatment with either pseudolaric acid B or adriamycin alone. Protein expression levels of cyclo-oxygenase-2, protein kinaseC-α and P-glycoprotein were inhibited by pseudolaric acid B alone or in combination with adriamycin in SGC7901/ADR cell xenografts.

CONCLUSION:

Pseudolaric acid B has a significant inhibitory effect and an additive inhibitory effect in combination with adriamycin on the growth of gastric cancer in vivo, which reverses the multidrug resistance of gastric neoplasm to chemotherapy drugs by downregulating the Cox-2/PKC-α/P-gp/mdr1 signaling pathway.

• Authors: Qian Sun, Yan Li
• Journal: PloS one (PLoS One) Vol. 9 Issue 9 Pg. e107830 ( 2014) ISSN: 1932-6203 [Electronic] United States
• PMID: 25250794 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• ATP Binding Cassette Transporter, Subfamily B
• Antibiotics, Antineoplastic
• Diterpenes
• Drugs, Chinese Herbal
• Doxorubicin
• pseudolaric acid B
• Cyclooxygenase 2
• Protein Kinase C-alpha

Topics

• ATP Binding Cassette Transporter, Subfamily B (analysis, metabolism)
• Adenocarcinoma (drug therapy, metabolism, pathology)
• Animals
• Antibiotics, Antineoplastic (pharmacology, therapeutic use)
• Cell Line, Tumor
• Cyclooxygenase 2 (analysis, metabolism)
• Diterpenes (pharmacology, therapeutic use)
• Doxorubicin (pharmacology, therapeutic use)
• Drug Resistance, Multiple (drug effects)
• Drug Resistance, Neoplasm (drug effects)
• Drugs, Chinese Herbal (pharmacology, therapeutic use)
• Female
• Humans
• Male
• Mice
• Mice, Nude
• Protein Kinase C-alpha (analysis, metabolism)
• Signal Transduction (drug effects)
• Stomach (drug effects, pathology)
• Stomach Neoplasms (drug therapy, metabolism, pathology)