Aim To observe the effect of the LSD1 gene on the proliferation and apoptosis of Molt-4 cells, a kind of human acute T-lymphoblastic leukemia cells. Methods siRNA fragment based on LSD1 gene was designed, filtered out and then transfected into Molt-4 cells. The effects of LSD 1 siRNA on Molt-4 cell prolif-eration were observed by the method of MTS. The cell apoptosis was analyzed by flow cytometry. The states of histone H3K4, H3K9 methylation, histone H3 acetyla-tion, p15, DNA methyltransferase 1 (DNMT1), and apoptosis-related proteins like Bcl-2 , procaspase-3 were evaluated by Western blot. Results Silencing LSD1 gene inhibited cell proliferation. Molt-4 cell pro-liferation rate was ( 99. 65 ± 1. 21 )%, ( 83. 02 ± 1. 69)%, (65. 72 ± 2. 16)%,and (41. 15 ± 2. 23)%respectively after the treatment of Molt-4 cells with 0 , 30, 60, 120 nmol·L-1 of LSD1 siRNA after 48 hours ( P < 0. 05 ) . Cell proliferation rate was ( 99. 86 ± 1. 35)%,(65. 72 ± 2. 16)%,(48. 26 ± 1. 92)%,and ( 37. 86 ± 1. 66 )% respectively after the transfection of Molt-4 cells with 60 nmol · L-1 of LSD1 siRNA after 0 , 24 , 48 , 72 hours ( P<0. 05 ) . Cell apoptosis rate was ( 3. 35 ± 1. 26 )%, ( 12. 16 ± 1. 74 )%, ( 32. 74 ± 2. 47 )%, ( 54. 64 ± 2. 58 )% respectively after transfection of LSD1 siRNA in indicated concentrations for 48 hours ( P <0. 05 ) . At the same time, the ex-pression levels of apoptosis-related proteins like Bcl-2 , procaspase-3 decreased. LSD1 siRNA inhibited LSD1 and LSD1 mRNA, and accumulated histone mono-, and di-methylation H3K4 and histone H3 acetylation. However, alteration of H3K4 trimethylation, H3K9 methylation was not detected. LSD1 siRNA downregu-lated DNA demethylase DNMT1 and upregulated p15 . Conclusions LSD1 siRNA can inhibit Molt-4 cell proliferation and induce apoptosis. Its mechanism may be associated with epigenetic regulation. In addition, it is expected to become a new target for leukemia treat-ment.

Aim To study the pharmacokinetics of curcumin-pvp solid dispersion ig administration in mice in comparison with the free curcumin suspension.Methods Drugs were administered at a dose of 300 mg?kg-1 via ig.The plasma concentration of curcumin was determined by HPLC,the pharmacokinetics were calculated by DAS ver1.0 program.Results The curcumin pharmacokinetics conforms to a two-compartment open model after a single ig dose of curcumin solid dispersion in mice.The parameters were as follows:T12? and T12? were 16.4 and 266.1 min,respectively.AUC was 89.6 mg?L-1?min-1,Vd was 763.9 L,V1 was 51.0 L,and CL was 1.99 L?min-1.The absorption rate of curcumin solid dispersion was 6.75 times as much as curcumin suspension.Conclusion The curcumin solid dispersion improves the absorption of curcumin in vivo in mice evidently.

Objective To study the distribution and pharmacokinetics of curcumin in tumor-bearing mice.Methods Curcumin injection(100 mg/kg)was injected to the tumor-bearing mice through tail vein.The liver,kidney,lung,heart,parenchymal tumor and ascitic fluid were acquired to abstract curcumin at 20,40,100 minutes after injection respectively.A HPLC method was established for determination of curcumin.Results Curcumin contents in the liver,kidney,lung,heart,parenchymal tumor and ascitic fluid were 6.40,0.98,0.13,0.06,0.05 and 0.02 ? g/g after injection of 20 minutes respectively.While after 40 minutes,the contents reduced to 0.20,0.06 and 0.02 ? g/g in the liver,kidney and lung respectively,and could not been detected in other tissues.After 100 minutes,curcumin was only detectable in the liver(0.04 ? g/g).Conclusion Curcumin distribution is focused in the liver of tumor-bearing mice,while the focal concentration is lower .Metabolism of curcumin in vivo is fast.

Objective To evaluate the anti-proliferation and anti-angiogenesis effect of curcumin-K30 solid dispersion (Cur-K30) on tumors in vivo. Methods Growth inhibition rates of the tumor cells was measured with MTT method. Tumor inhibition was detected by tumors transplanted subcutaneously in mice treated with Cur-K30 ［50， 100， and 200 mg/(kg·d)］. The expressions of CD34 and vascular endothelial growth factor (VEGF) were assessed by immunohistochemical study, and analyzed by Imageproplus software. Results Cur-K30 had inhibitory effect on different tumor cell lines in a dose dependent manner with IC50 values from 6.6 to 12.12 μg/mL. The in vivo study showed that the inhibitory rates of the 200 mg/(kg·d) Cur-K30 group on H22, B16, and SW480 were 43.2%, 53.1%, and 59.8%, respectively, which were all much higher than the inhibitory rates of curcumin suspension group with the same dose. Compared with the control group， the expression of CD34 and VEGF in SW480 tumors was down-regulated in the 200 mg/(kg·d) Cur-K30 group (P<0.01). Conclusion The proliferation inhibition of Cur-K30 is higher than curcumin in vivo， and the most significant effect is obtained in SW480 tumors transplanted subcutaneously in nude mice. Down-regulation of VEGF and decreased microvascular density may contribute to the anti-tumor effect of Cur-K30.