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Repeated administration of inhibitors for ion pumps reduce markedly tumor growth in vivo.

Hrgovic I, Glavic Z, Kovacic Z, Mulic S, Zunic L, Hrgovic Z - Med Arch (2014)

Bottom Line: Considering the rate of survival a statistically significant difference between treated and untreated animals was observed.The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation.Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives.

Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum.

Results: After termination of the experiments the mean tumor diameter in the control group was 12.4 +/- 0.8mm, in group A it was 6.9 +/- 0.6mm, and in group B we measured 6.6 +/- 3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment.

Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options.

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The mean tumor diameter was in all treated groups significantly lowered after day 6, respectively after the third injection of inhibitors (p<0.0005).
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Figure 1: The mean tumor diameter was in all treated groups significantly lowered after day 6, respectively after the third injection of inhibitors (p<0.0005).

Mentions: At the beginning of the series of experiments the mean tumor diameter in the control group was 9.0±0.9mm. Tumor diameter in group A was 8.4±0.6mm, in group B it was 8.6±0.8mm, and in group C it was 8.2±1.9mm. Between the different groups were no statistically relevant alterations concerning tumor size. According to the protocol we injected during 18 days inhibitors of ion pumps and physiologic solutions, respectively, into the tumors. The mean tumor diameter was in group A, B and C significantly lowered after day 6, respectively after the third injections of inhibitors (p<0.005) (Figure 1).


Repeated administration of inhibitors for ion pumps reduce markedly tumor growth in vivo.

Hrgovic I, Glavic Z, Kovacic Z, Mulic S, Zunic L, Hrgovic Z - Med Arch (2014)

The mean tumor diameter was in all treated groups significantly lowered after day 6, respectively after the third injection of inhibitors (p<0.0005).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4291850&req=5

Figure 1: The mean tumor diameter was in all treated groups significantly lowered after day 6, respectively after the third injection of inhibitors (p<0.0005).
Mentions: At the beginning of the series of experiments the mean tumor diameter in the control group was 9.0±0.9mm. Tumor diameter in group A was 8.4±0.6mm, in group B it was 8.6±0.8mm, and in group C it was 8.2±1.9mm. Between the different groups were no statistically relevant alterations concerning tumor size. According to the protocol we injected during 18 days inhibitors of ion pumps and physiologic solutions, respectively, into the tumors. The mean tumor diameter was in group A, B and C significantly lowered after day 6, respectively after the third injections of inhibitors (p<0.005) (Figure 1).

Bottom Line: Considering the rate of survival a statistically significant difference between treated and untreated animals was observed.The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation.Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals.

View Article: PubMed Central - PubMed

ABSTRACT

Introduction: Measurements of extracellular pH show that the micro environment of malignant tumors is more acidic than that of normal cells, whereas pH does not differ appreciable in normal and malignant cells. The acid micro environment of tumors is created by the secretion of tumor factors and ATP hydrolysis in hypoxic tumor tissue. In order to survive in a low pH-environment tumor cells develop regulatory mechanisms which keep their intracellular pH stable. Two of the most important systems are the Na+/H+ ion pump and the Na-dependent HCO3-/Cl- pump of stilbenian derivatives.

Material and methods: Experiments were carried out on DBA mice of both sexes at the age of 4 month. Laboratory animals were grown in our institute and supplied with food and aqua ad libitum.

Results: After termination of the experiments the mean tumor diameter in the control group was 12.4 +/- 0.8mm, in group A it was 6.9 +/- 0.6mm, and in group B we measured 6.6 +/- 3.1mm. At the final day the tumor size in treated animals was twice as small as in the control group. In addition we observed the rate of survival. In the control group only 18% of the animals were still alive at day 18. Considering the rate of survival a statistically significant difference between treated and untreated animals was observed. The survival of tumor cells is dependent on the function of these ion pumps which keep their intracellular pH values constant in the setting of an acid extracellular environment.

Conclusion: The activity of the ion pump is especially important at the beginning of cell division and in cell proliferation. Our in vivo experiments demonstrate that prolonged administration of intratumoral ion pump inhibitors suppresses tumor growth as well as enhances survival of tumor-bearing animals. Research of inhibitors of ion pumps and their action in tumor growth opens new perspectives into pathophysiology of malignant tumors and may create new therapeutic options.

Show MeSH
Related in: MedlinePlus