Abstract
Objectives:
Pancreatic carcinoma is one of the most aggressive cancers overcoming chemoresistance. Thus, novel compounds to complement the current antitumor agents are in need. Ocoxin oral solution (OOS) has proven antioxidant, anti-inflammatory, and antistromagenic properties. The aim of this study was to analyze the effect of OOS in an experimental pancreatic cancer model and its implication in stroma-related chemoresistance to paclitaxel and gemcitabine.
Methods:
Murine pancreatic carcinoma 266-6 cells were treated with OOS to analyze cell cycle and to perform a mRNA comparative microarray study. Then the viability was assessed in combination with paclitaxel and/or gemcitabine. Chemoresistance induced by the medium taken from fibroblast cultures was also investigated on 6 human pancreatic carcinoma cell lines. Furthermore, an experimental model of pancreatic cancer was carried out to study the effect of OOS in vivo.
Results:
Ocoxin oral solution enhances the cytotoxic effect of paclitaxel and gemcitabine, while it ameliorates the chemoresistance induced by fibroblast-derived soluble factors in human pancreatic cancer cells. The OOS also promotes the regulation of the expression of genes that are altered in pancreatic carcinoma and slows down 266-6 cell pancreatic tumor development in vivo.
Conclusions:
Ocoxin oral solution could be a potential complement to the chemotherapeutic drugs for pancreatic adenocarcinoma.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adenocarcinoma / drug therapy*
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Adenocarcinoma / genetics
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Adenocarcinoma / pathology
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Administration, Oral
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Animals
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Antineoplastic Agents / administration & dosage
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Antineoplastic Agents / pharmacology
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Ascorbic Acid / administration & dosage
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Ascorbic Acid / pharmacology*
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Cell Cycle / drug effects
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Cell Cycle / genetics
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Cell Line
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Cell Line, Tumor
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Cell Survival / drug effects
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Cell Survival / genetics
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Deoxycytidine / administration & dosage
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Deoxycytidine / analogs & derivatives
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Deoxycytidine / pharmacology
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Drug Resistance, Neoplasm / drug effects*
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Drug Resistance, Neoplasm / genetics
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Folic Acid
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Gemcitabine
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Gene Expression Profiling
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Gene Expression Regulation, Neoplastic / drug effects
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Humans
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Male
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Mice, Inbred C57BL
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Neoplasms, Experimental / drug therapy*
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Neoplasms, Experimental / genetics
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Neoplasms, Experimental / pathology
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Paclitaxel / administration & dosage
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Paclitaxel / pharmacology
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Pancreatic Neoplasms / drug therapy*
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Pancreatic Neoplasms / genetics
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Pancreatic Neoplasms / pathology
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Pantothenic Acid
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Plant Extracts / administration & dosage
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Plant Extracts / pharmacology*
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Solutions
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Vitamin B 12 / administration & dosage
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Vitamin B 12 / pharmacology*
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Vitamin B 6 / administration & dosage
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Vitamin B 6 / pharmacology*
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Zinc Sulfate
Substances
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Antineoplastic Agents
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Ocoxin
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Plant Extracts
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Solutions
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Deoxycytidine
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Pantothenic Acid
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Zinc Sulfate
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Vitamin B 6
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Folic Acid
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Vitamin B 12
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Paclitaxel
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Ascorbic Acid
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Gemcitabine