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Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

Yu M, Lee C, Wang M, Tannock IF - Cancer Sci. (2015)

Bottom Line: We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin.To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models.Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone.

View Article: PubMed Central - PubMed

Affiliation: Ontario Cancer Institute, Toronto, Ontario, Canada.

No MeSH data available.


Related in: MedlinePlus

Distribution of doxorubicin fluorescence intensity in relation to blood vessels in EMT6- and MCF7-derived tumors. Mice were given either 25 mg/kg doxorubicin alone ((Dox; 10 min) (a, d) or 200 mg/kg lansoprazole (2 h before doxorubicin) and doxorubicin (Dox+Lanso) (b, e) prior to tumor excision. Tumors were imaged and quantified using a customized algorithm to show the mean absolute (background-subtracted) values of doxorubicin fluorescence intensity (blue) as a function of distance to the nearest functional blood vessel (green) (c, f). Scale bar = 100 μm.
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fig04: Distribution of doxorubicin fluorescence intensity in relation to blood vessels in EMT6- and MCF7-derived tumors. Mice were given either 25 mg/kg doxorubicin alone ((Dox; 10 min) (a, d) or 200 mg/kg lansoprazole (2 h before doxorubicin) and doxorubicin (Dox+Lanso) (b, e) prior to tumor excision. Tumors were imaged and quantified using a customized algorithm to show the mean absolute (background-subtracted) values of doxorubicin fluorescence intensity (blue) as a function of distance to the nearest functional blood vessel (green) (c, f). Scale bar = 100 μm.

Mentions: The potential effects of lansoprazole to modify doxorubicin distribution in relation to functional blood vessels were evaluated in transplanted tumors derived from EMT6 and MCF7 cells. Ten minutes after injection, distribution of doxorubicin in EMT6 and MCF7 tumors treated with doxorubicin alone was poor and was limited to perivascular regions; there was a rapid decline in doxorubicin fluorescence intensity with increasing distance from blood vessels (Fig.4a,d). Pretreatment with lansoprazole led to a substantial increase in doxorubicin fluorescence, particularly in areas situated distant from blood vessels, in both EMT6 and MCF7 tumors compared with those exposed to doxorubicin alone (Fig.4b,e). Quantification of the doxorubicin distribution at 10 min after injection showed steep gradients of reducing doxorubicin fluorescence relative to distance from the nearest functional blood vessel in all tumors (Fig.4c,f). A significantly shallower gradient of reducing doxorubicin intensity was identified in EMT6 tumors pretreated with lansoprazole when compared with tumors treated with doxorubicin alone (P < 0.05; Fig.4c). A similar trend was also seen in MCF7 tumors pretreated with lansoprazole compared to those in the doxorubicin only group, although the difference in drug distribution between the two treatment groups was not statistically significant (Fig.4f).


Influence of the proton pump inhibitor lansoprazole on distribution and activity of doxorubicin in solid tumors.

Yu M, Lee C, Wang M, Tannock IF - Cancer Sci. (2015)

Distribution of doxorubicin fluorescence intensity in relation to blood vessels in EMT6- and MCF7-derived tumors. Mice were given either 25 mg/kg doxorubicin alone ((Dox; 10 min) (a, d) or 200 mg/kg lansoprazole (2 h before doxorubicin) and doxorubicin (Dox+Lanso) (b, e) prior to tumor excision. Tumors were imaged and quantified using a customized algorithm to show the mean absolute (background-subtracted) values of doxorubicin fluorescence intensity (blue) as a function of distance to the nearest functional blood vessel (green) (c, f). Scale bar = 100 μm.
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4638015&req=5

fig04: Distribution of doxorubicin fluorescence intensity in relation to blood vessels in EMT6- and MCF7-derived tumors. Mice were given either 25 mg/kg doxorubicin alone ((Dox; 10 min) (a, d) or 200 mg/kg lansoprazole (2 h before doxorubicin) and doxorubicin (Dox+Lanso) (b, e) prior to tumor excision. Tumors were imaged and quantified using a customized algorithm to show the mean absolute (background-subtracted) values of doxorubicin fluorescence intensity (blue) as a function of distance to the nearest functional blood vessel (green) (c, f). Scale bar = 100 μm.
Mentions: The potential effects of lansoprazole to modify doxorubicin distribution in relation to functional blood vessels were evaluated in transplanted tumors derived from EMT6 and MCF7 cells. Ten minutes after injection, distribution of doxorubicin in EMT6 and MCF7 tumors treated with doxorubicin alone was poor and was limited to perivascular regions; there was a rapid decline in doxorubicin fluorescence intensity with increasing distance from blood vessels (Fig.4a,d). Pretreatment with lansoprazole led to a substantial increase in doxorubicin fluorescence, particularly in areas situated distant from blood vessels, in both EMT6 and MCF7 tumors compared with those exposed to doxorubicin alone (Fig.4b,e). Quantification of the doxorubicin distribution at 10 min after injection showed steep gradients of reducing doxorubicin fluorescence relative to distance from the nearest functional blood vessel in all tumors (Fig.4c,f). A significantly shallower gradient of reducing doxorubicin intensity was identified in EMT6 tumors pretreated with lansoprazole when compared with tumors treated with doxorubicin alone (P < 0.05; Fig.4c). A similar trend was also seen in MCF7 tumors pretreated with lansoprazole compared to those in the doxorubicin only group, although the difference in drug distribution between the two treatment groups was not statistically significant (Fig.4f).

Bottom Line: We determined the effects of the PPI lansoprazole to modify the activity of doxorubicin.To gain insight into its mechanisms, we studied the effects of lansoprazole on endosomal pH, and on the spatial distribution of doxorubicin, and of biomarkers reflecting its activity, using in vitro and murine models.Combined treatment with lansoprazole and doxorubicin was more effective in delaying tumor growth as compared to either agent alone.

View Article: PubMed Central - PubMed

Affiliation: Ontario Cancer Institute, Toronto, Ontario, Canada.

No MeSH data available.


Related in: MedlinePlus