[Preliminary study for the roles and mechanisms of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles in the Lewis lung cancer mice].
OBJECTIVE
To comparatively observe the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on the Lewis lung cancer mice and to explore the mechanisms of Rg3 and PEG-PLGA-Rg3 nanoparticle anti-cancer in vivo.


METHODS
Lewis lung cancer mouse model was established and 60 mice were randomly divided into 5 groups with twelve in each group: PEG-PLGA-Rg3 nanoparticles group(Rg3-N), PEG-PLGA group (PEG), Rg3 group (Rg3), normal control group(C), saline control group(NS), and received intragastric administration for 14 days. The weights of the mice were measured every 2 days and the weight curves were obtained. At the same time, the color pattern, activity and mental status were observed. The mice were sacrificed when the administration was over, and the effects of 20(R)-ginsenoside Rg3 and PEG-PLGA-Rg3 nanoparticles on tumor weight, and the tumor:weight ratios were analysed. In addition, the tumor microvessel density (MVD) was measured by immunohistochemical staining with anti-CD31 antibody to compare the effects of Rg3 and PEG-PLGA-Rg3 nanoparticles on the tumor angiogenesis in vivo. Furthermore, the levels of such angiogenesis and proliferation factors as MMP-9, HIF-1α, VEGF, Ki-67 were examined by RT-PCR, Western blot and immunohistochemistry to explore the internal molecular mechanisms of anti-tumor effects in vivo.


RESULTS
The trends of variation of the mice weights in NS group and PEG group were rising early but declining later. In contrast, the trends of the other three groups were rising early and became stable later. In comparison with NS group, the mice of Rg3 group and Rg3-N group had better general status: brighter color, more active and better spirit. Compared with NS group,the tumor weight in PEG group, Rg3 group and Rg3-N group showed no significant difference but the tumor:weight ratio and MVD in Rg3 group and Rg3-N group declined significantly (P<0.01). Besides, there was no significant difference between Rg3 group and Rg3-N group. At the same time, the level of VEGF mRNA, the protein expression of MMP-9, HIF-1α, VEGF in Rg3 group and Rg3-N group decreased compared with NS group. Furthermore, the level of each index above-mentioned in Rg3-N group was lower than that in Rg3 group. The expression of Ki-67 in PEG group, Rg3 group and Rg3-N group showed no significant difference compared with NS group.


CONCLUSIONS
Rg3 and PEG-PLGA-Rg3 nanoparticle may suppress the expression of VEGF, MMP-9 and HIF-1α in Lewis lung cancer mice, thereby indirectly contributing to their antitumor effects and alleviating the mice's general status. In addition, PEG-PLGA nanoparticles embedding can promote Rg3 antitumor effect in vivo.
Department of Integrated Chinese and Westem Medicine, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
L
L
Geng
Henan University of Chinese Medicine, Zhengzhou, 450008, China.
J
J
Fan
Department of Integrated Chinese and Westem Medicine, Cancer Hospital Affiliated to Zhengzhou University, Henan Cancer Hospital, Zhengzhou 450008, China.
Q L
QL
Gao
Department of Oncology, Beijing Friendship Hospital Affiliated to Capital Medical University, Beijing 100050, China.
J
J
Yu
Department of Oncology, Guang'anmen Hospital, China Academy of Chinese Medical Sciences,Beijing 100053,China.
B J
BJ
Hua
D000818:Animals; D004195:Disease Models, Animal; D036145:Ginsenosides / Q000494:pharmacology*; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism; D019394:Ki-67 Antigen / Q000378:metabolism; D008175:Lung Neoplasms / Q000188:drug therapy*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D053758:Nanoparticles / Q000737:chemistry; D009389:Neovascularization, Pathologic; D011091:Polyesters / Q000737:chemistry; D011092:Polyethylene Glycols / Q000737:chemistry; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
D036145:Ginsenosides; C497443:Hif1a protein, mouse; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D019394:Ki-67 Antigen; D011091:Polyesters; D042461:Vascular Endothelial Growth Factor A; C000589473:polyethylene glycol-poly(lactide-co-glycolide); C467480:vascular endothelial growth factor A, mouse; C097367:ginsenoside Rg3; D011092:Polyethylene Glycols; D020780:Matrix Metalloproteinase 9; C501830:Mmp9 protein, mouse