In vitro and in vivo antitumor activity of oridonin nanosuspension.
The aim of the present study was to evaluate the antitumor activity of an oridonin (ORI) nanosuspension relative to ORI solution both in vitro and in vivo. ORI nanosuspension with a particle size of 897.2+/-14.2 nm was prepared by the high pressure homogenization method (HPH). MTT assay showed that ORI nanosuspension could significantly enhance the in vitro cytotoxicity against K562 cells compared to the ORI solution, the IC(50) value at 36 h was reduced from 12.85 micromol/L for ORI solution to 8.11 micromol/L for ORI nanosuspension. Flow cytometric analysis demonstrated that the ORI nanosuspension also induced a higher apoptotic rate in K562 cells compared to ORI solution. In vivo studies in a mouse model of sarcoma-180 solid tumors demonstrated significantly greater inhibition of tumor growth following treatment with ORI nanosuspension than ORI solution at the same dosage. The mice injected with ORI nanosuspension showed a higher reduction in tumor volume and tumor weight at the dose of 20mg/kg compared to the ORI solution (P<0.01), with the tumor inhibition rate increased from 42.49% for ORI solution to 60.23% for the ORI nanosuspension. Taken together, these results suggest that the delivery of ORI in nanosuspension is a promising approach for the treatment of the tumor.
Lou
Haiyan
H
Department of Pharmacology, School of Medicine, Shandong University, No. 44 Wenhuaxi Road, Jinan 250012, China.
Zhang
Xiumei
X
Gao
Lei
L
Feng
Feifei
F
Wang
Juying
J
Wei
Xinbing
X
Yu
Zongqin
Z
Zhang
Dianrui
D
Zhang
Qiang
Q
D000818:Animals; D000972:Antineoplastic Agents, Phytogenic / Q000008:administration & dosage / Q000494:pharmacology*; D017209:Apoptosis; D045786:Diterpenes, Kaurane / Q000008:administration & dosage / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D020128:Inhibitory Concentration 50; D020014:K562 Cells; D051379:Mice; D053758:Nanoparticles; D010316:Particle Size; D012510:Sarcoma 180 / Q000188:drug therapy*; D013535:Suspensions
D000972:Antineoplastic Agents, Phytogenic; D045786:Diterpenes, Kaurane; D013535:Suspensions; C011959:oridonin