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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

Ability of quinine to inhibit expression of P-gp in A549/T, MCF-7/A, and HCT-8/V cells using the Western blot assay.Note: Concentrations of quinine were 5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL.Abbreviation: P-gp, P-glycoprotein.
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f3-ijn-10-4225: Ability of quinine to inhibit expression of P-gp in A549/T, MCF-7/A, and HCT-8/V cells using the Western blot assay.Note: Concentrations of quinine were 5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL.Abbreviation: P-gp, P-glycoprotein.

Mentions: The expression levels of P-gp in A549/T, MCF-7/A, and HCT-8/V cells were analyzed using Western blotting in order to confirm whether QN could downregulate P-gp expression. As shown in Figure 3, P-gp expression was greatly inhibited by QN treatment in a concentration-dependent manner in all three cell lines. The results demonstrated that QN could downregulate P-gp expression. This is another reason why QN can sensitize drug-resistant cancer cells 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)

Ability of quinine to inhibit expression of P-gp in A549/T, MCF-7/A, and HCT-8/V cells using the Western blot assay.Note: Concentrations of quinine were 5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL.Abbreviation: P-gp, P-glycoprotein.
© Copyright Policy
Related In: Results  -  Collection

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

f3-ijn-10-4225: Ability of quinine to inhibit expression of P-gp in A549/T, MCF-7/A, and HCT-8/V cells using the Western blot assay.Note: Concentrations of quinine were 5 µg/mL, 10 µg/mL, 25 µg/mL, 50 µg/mL, and 100 µg/mL.Abbreviation: P-gp, P-glycoprotein.
Mentions: The expression levels of P-gp in A549/T, MCF-7/A, and HCT-8/V cells were analyzed using Western blotting in order to confirm whether QN could downregulate P-gp expression. As shown in Figure 3, P-gp expression was greatly inhibited by QN treatment in a concentration-dependent manner in all three cell lines. The results demonstrated that QN could downregulate P-gp expression. This is another reason why QN can sensitize drug-resistant cancer cells 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