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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

Histopathology of tumors.Notes: Hematoxylin/eosin staining of tumors treated with various groups at a VCR concentration of 1 mg/kg and a QN concentration of 2 mg/kg.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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f8-ijn-10-4225: Histopathology of tumors.Notes: Hematoxylin/eosin staining of tumors treated with various groups at a VCR concentration of 1 mg/kg and a QN concentration of 2 mg/kg.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: To further assess the damage induced by the treatments, we conducted hematoxylin and eosin staining of tumor sections from each treatment group (Figure 8). The nuclei are stained with hematoxylin (blue) while the other parts of the cell are stained with eosin (red and pink). In control tumor tissue sections, the tumor cell nuclei were large with prominent nucleoli, and only a few cells showed reduced nuclear size with deeply stained nuclei and condensed cytoplasm. In contrast, in the combination treatment groups, a greater number of cells had hyperchromatic nuclei and a reduced nuclear size, especially in the VQL1:2 group.


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

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

Histopathology of tumors.Notes: Hematoxylin/eosin staining of tumors treated with various groups at a VCR concentration of 1 mg/kg and a QN concentration of 2 mg/kg.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

f8-ijn-10-4225: Histopathology of tumors.Notes: Hematoxylin/eosin staining of tumors treated with various groups at a VCR concentration of 1 mg/kg and a QN concentration of 2 mg/kg.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: To further assess the damage induced by the treatments, we conducted hematoxylin and eosin staining of tumor sections from each treatment group (Figure 8). The nuclei are stained with hematoxylin (blue) while the other parts of the cell are stained with eosin (red and pink). In control tumor tissue sections, the tumor cell nuclei were large with prominent nucleoli, and only a few cells showed reduced nuclear size with deeply stained nuclei and condensed cytoplasm. In contrast, in the combination treatment groups, a greater number of cells had hyperchromatic nuclei and a reduced nuclear size, especially in the VQL1:2 group.

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