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Abstract

LACTATE TRANSPORT AND ACIDOSIS AS TARGET FOR TUMOR REGRESSION BY DRUG REPOSITIONING IN LUNG CARCINOGENESIS MODEL

M. S. Sarankumar* and A. Suresh

ABSTRACT

Objective: The objective of the present study was to inhibit the lactate transport and acidosis by using atorvastatin, pantoprazole and sodium bicarbonate in urethane induced lung carcinogenesis model Method: The day of starting the experiment, the animals were divided in to 5 groups for six animals each. The group I serve as control and group II serves as negative control receive 600mg/kg urethane and group III, group IV and group V serve as treatment groups receive atorvastatin (10mg/kg), pantoprazole (20mg/kg) and sodium bicarbonate (200mmol/L) respectively from the day of urethane administration once daily orally for 26 weeks. . During the period of study the body weight of the animal were recorded. At the end of the study blood samples are collected by retro orbital puncture and evaluate the tumor marker, inflammatory marker, blood lactate pyruvate LDH and glucose. After blood collection, the lung immediately excised and washed with ice cold saline and weighed to calculated the relative lung weight and lung tissue were used to evaluate the tissue lactate, pyruvate and SDH. The portion of the lung tissue was subjected to histopathological examination to evaluate the microscopical changes in the tissue. Result: In this present study, groups of animal treated with atorvastatin, pantoprazole and sodium bicarbonate showed a significant decrease in cancer incidence with decrease in tumor load, tumor volume and multiplicity compared with cancer control. The markers of glycolytic stress were significantly decreased and SDH levels were significantly increased compared to cancer control. The histpathology of lung supported the biochemical parameters, showed inflammatory infiltrates without any incidence of neoplastic cells. Conclusion: From the result, it was observed that atorvastatin, pantoprazole and sodium bicarbonate showed a significant protection against urethane induced lung carcinogenesis. This might be due to inhibition of mono-carboxylate transporters and metabolic acidosis in cancer cells. These finding provide new evidence for the mechanism by which this class of drugs may be acting on cancer cells.

Keywords: Anti-cancer activity, Urethane, Atorvastatin, Pantoprazole, Sodium bicarbonate, Mono-carboxylate transporter.


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