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Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes.

Xu Y, Qiu L - Int J Nanomedicine (2015)

Bottom Line: The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice.The results of this in vivo study indicated that VQL could reverse VCR resistance.In addition, it reduced tumor volume 5.4-fold when compared with other test groups.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.

ABSTRACT
The use of vincristine (VCR) to treat cancer has been limited by its dose-dependent toxicity and development of drug resistance after repeated administrations. In this study, we investigated the mechanism by which quinine hydrochloride (QN) acts as a sensitizer for VCR. Our experiments used three kinds of multidrug-resistant cancer cells and demonstrated that QN worked by inducing intracellular depletion of adenosine triphosphate, increasing adenosine triphosphatase activity, and decreasing P-glycoprotein expression. Based on these results, we designed and prepared a VCR and QN codelivery liposome (VQL) and investigated the effect of coencapsulated QN on the in vitro cytotoxicity of VCR in cells and three-dimensional multicellular tumor spheroids. The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice. The results of this in vivo study indicated that VQL could reverse VCR resistance. In addition, it reduced tumor volume 5.4-fold when compared with other test groups. The data suggest that VQL could be a promising nanoscaled therapeutic agent to overcome multidrug resistance, and may have important clinical implications for the treatment of cancer.

No MeSH data available.


Related in: MedlinePlus

Effect of quinine on cellular adenosine triphosphate levels in A549/T, MCF-7/A, and HCT-8/V cells.Note: Cells were incubated with quinine in a series of concentrations at 150, 100, 50, 25, 10, and 5 µg/mL for 4 hours.
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f2-ijn-10-4225: Effect of quinine on cellular adenosine triphosphate levels in A549/T, MCF-7/A, and HCT-8/V cells.Note: Cells were incubated with quinine in a series of concentrations at 150, 100, 50, 25, 10, and 5 µg/mL for 4 hours.

Mentions: As shown in Figure 2, the level of ATP was significantly and dose-dependently decreased as QN concentration increased. As discussed above, QN has a strong affinity for P-gp. A strong depletion of cellular energy would be associated with active efflux of QN in drug-resistant cancer cells, which would further inhibit the efflux of other drugs such as VCR. Therefore, it is reasonable to assume that the competition between QN and VCR to bind with P-gp leads to reversal of drug resistance to VCR.


Nonspecifically enhanced therapeutic effects of vincristine on multidrug-resistant cancers when coencapsulated with quinine in liposomes.

Xu Y, Qiu L - Int J Nanomedicine (2015)

Effect of quinine on cellular adenosine triphosphate levels in A549/T, MCF-7/A, and HCT-8/V cells.Note: Cells were incubated with quinine in a series of concentrations at 150, 100, 50, 25, 10, and 5 µg/mL for 4 hours.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4494179&req=5

f2-ijn-10-4225: Effect of quinine on cellular adenosine triphosphate levels in A549/T, MCF-7/A, and HCT-8/V cells.Note: Cells were incubated with quinine in a series of concentrations at 150, 100, 50, 25, 10, and 5 µg/mL for 4 hours.
Mentions: As shown in Figure 2, the level of ATP was significantly and dose-dependently decreased as QN concentration increased. As discussed above, QN has a strong affinity for P-gp. A strong depletion of cellular energy would be associated with active efflux of QN in drug-resistant cancer cells, which would further inhibit the efflux of other drugs such as VCR. Therefore, it is reasonable to assume that the competition between QN and VCR to bind with P-gp leads to reversal of drug resistance to VCR.

Bottom Line: The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice.The results of this in vivo study indicated that VQL could reverse VCR resistance.In addition, it reduced tumor volume 5.4-fold when compared with other test groups.

View Article: PubMed Central - PubMed

Affiliation: College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, People's Republic of China.

ABSTRACT
The use of vincristine (VCR) to treat cancer has been limited by its dose-dependent toxicity and development of drug resistance after repeated administrations. In this study, we investigated the mechanism by which quinine hydrochloride (QN) acts as a sensitizer for VCR. Our experiments used three kinds of multidrug-resistant cancer cells and demonstrated that QN worked by inducing intracellular depletion of adenosine triphosphate, increasing adenosine triphosphatase activity, and decreasing P-glycoprotein expression. Based on these results, we designed and prepared a VCR and QN codelivery liposome (VQL) and investigated the effect of coencapsulated QN on the in vitro cytotoxicity of VCR in cells and three-dimensional multicellular tumor spheroids. The antitumor effects of the formulation were also evaluated in multidrug-resistant tumor-bearing mice. The results of this in vivo study indicated that VQL could reverse VCR resistance. In addition, it reduced tumor volume 5.4-fold when compared with other test groups. The data suggest that VQL could be a promising nanoscaled therapeutic agent to overcome multidrug resistance, and may have important clinical implications for the treatment of cancer.

No MeSH data available.


Related in: MedlinePlus