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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

Morphological changes in A549/T multicellular tumor spheroids and MCF-7/ADR multicellular tumor spheroids.Notes: Multicellular tumor spheroids were treated with various drugs and formulations with the same concentration (150 µg/mL) of VCR for 7 days. The scale bar represents 500 μm.Abbreviations: VCR, vincristine; QN, quinine; FVCR, free vincristine; FQN, free quinine; F1:2, free vincristine + free quinine =1:2; VCRL, VCR liposome; QNL, QN liposome; L1:2, VCR liposome + QN liposome =1:2; VQL1:2, VCR and QN codelivery liposome with a ratio of 1:2.
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f6-ijn-10-4225: Morphological changes in A549/T multicellular tumor spheroids and MCF-7/ADR multicellular tumor spheroids.Notes: Multicellular tumor spheroids were treated with various drugs and formulations with the same concentration (150 µg/mL) of VCR for 7 days. The scale bar represents 500 μm.Abbreviations: VCR, vincristine; QN, quinine; FVCR, free vincristine; FQN, free quinine; F1:2, free vincristine + free quinine =1:2; VCRL, VCR liposome; QNL, QN liposome; L1:2, VCR liposome + QN liposome =1:2; VQL1:2, VCR and QN codelivery liposome with a ratio of 1:2.

Mentions: In this study, we used inverted microscopy to investigate the effect of VCR and QN combination therapy on MTS (Figure 6). After 7 days of treatment, the MTS of A549/T cells and MCF-7/A cells in the control group had barely changed. No significant difference in the growth of MTS was observed relative to the untreated control group after treatment with FVCR, FQN, VCR liposomes, or QN liposomes. In the case of MCF-7/A MTS, L1:2 treatment did not reduce the volume of MTS, while VQL1:2 did. The growth of MCF-7/A and A549/T MTS was completely impeded following incubation with VQL1:2 at a VCR concentration of 150 µg/mL. These morphological characteristics indicated that VCR and QN coloaded liposome therapy has a strong anticancer effect.


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

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

Morphological changes in A549/T multicellular tumor spheroids and MCF-7/ADR multicellular tumor spheroids.Notes: Multicellular tumor spheroids were treated with various drugs and formulations with the same concentration (150 µg/mL) of VCR for 7 days. The scale bar represents 500 μm.Abbreviations: VCR, vincristine; QN, quinine; FVCR, free vincristine; FQN, free quinine; F1:2, free vincristine + free quinine =1:2; VCRL, VCR liposome; QNL, QN liposome; L1:2, VCR liposome + QN liposome =1:2; VQL1:2, VCR and QN codelivery liposome with a ratio of 1:2.
© Copyright Policy
Related In: Results  -  Collection

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

f6-ijn-10-4225: Morphological changes in A549/T multicellular tumor spheroids and MCF-7/ADR multicellular tumor spheroids.Notes: Multicellular tumor spheroids were treated with various drugs and formulations with the same concentration (150 µg/mL) of VCR for 7 days. The scale bar represents 500 μm.Abbreviations: VCR, vincristine; QN, quinine; FVCR, free vincristine; FQN, free quinine; F1:2, free vincristine + free quinine =1:2; VCRL, VCR liposome; QNL, QN liposome; L1:2, VCR liposome + QN liposome =1:2; VQL1:2, VCR and QN codelivery liposome with a ratio of 1:2.
Mentions: In this study, we used inverted microscopy to investigate the effect of VCR and QN combination therapy on MTS (Figure 6). After 7 days of treatment, the MTS of A549/T cells and MCF-7/A cells in the control group had barely changed. No significant difference in the growth of MTS was observed relative to the untreated control group after treatment with FVCR, FQN, VCR liposomes, or QN liposomes. In the case of MCF-7/A MTS, L1:2 treatment did not reduce the volume of MTS, while VQL1:2 did. The growth of MCF-7/A and A549/T MTS was completely impeded following incubation with VQL1:2 at a VCR concentration of 150 µg/mL. These morphological characteristics indicated that VCR and QN coloaded liposome therapy has a strong anticancer effect.

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