The purpose of this study was to investigate the potential antitumor efficacy of conjugated linoleic acid-paclitaxel （CLA-PTX） on B16-F10 melanoma cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis and cell cycle of CLA-PTX were investigated. The in vitro cellular uptake of CLA-PTX in B16-F10 cells was also analyzed. The antitumor activity of CLA-PTX was also evaluated in B16-F10 tumor-bearing C57BL6/N mice in vivo. The in vitro cytotoxicity results showed that the IC50 of the CLA-PTX is （4.25±0.43） μM, compared with that of （6.70±0.80） μM in PTX treatment group （P〈0.01）. CLA-PTX increased the percentage of total apoptotic cells compared with that of control and PTX treatment groups （P〈0.01）. Compared with untreated cells, CLA-PTX arrested cell cycle progression at the S phase, whereas PTX caused accumulation of cell at GE-M phase both along with the reduction of the cellular fraction arrested at the G1 phase. The amount of cellular uptake of CLA-PTX was significantly higher than that of PTX （P〈0.01）. The in vivo antitumor activity of CLA-PTX was significantly higher than that of control and PTX treatment groups （P〈0.01 or P〈0.05）. In conclusion, our study demonstrated that CLA-PTX has significant antitumor activity in B 16-F 10 cell line.
In the present study, we prepared the iRGD-modified lysolipid-containing thermosensitive liposomes(LTSL) containing conjugated linoleic acid-paclitaxel(CLA-PTX), also known as iRGD-LTSL-CLA-PTX. The in vitro cellular uptake and in vitro cytotoxicity of iRGD-LTSL-CLA-PTX were evaluated in B16-F10 melanoma cells. The in vivo anti-tumor effect of i RGD-LTSL-CLA-PTX was investigated using B16-F10 tumor-bearing C57BL/6 mice. The results of the cellular uptake experiment indicated that the increased cellular uptake of CLA-PTX in the iRGD-LTSL-CLA-PTX-treated groups was 2.05-, 3.31-or 4.83-fold compared with that in the SSL-CLA-PTX group after a 2-, 4-or 6-h incubation at 42 °C, respectively. The in vivo antitumor results showed that iRGD-LTSL-CLA-PTX/heat significantly inhibited the growth of B16-F10 tumors compared with the CLA-PTX solution(LTSL-CLA-PTX, LTSL-CLA-PTX/heat and iRGD-LTSL-CLA-PTX)(P<0.01). In conclusion, the antitumor effect of iRGD-LTSL-CLA-PTX was confirmed on B16-F10 melanoma in vitro and in vivo, which was induced by both the effect of iRGD and LTSL.
Considering the results of our previous research that conjugated linoleic acid mixture-paclitaxel （CLA-mixture-PTX） possesses anti-tumor activity against melanoma and brain glioma, the purpose of this study was to investigate the potential anti-tumor efficacy of cis-9, trans- 1 1-conjugated linoleic acid-paclitaxel （c9, tl 1-CLA-PTX） and trans- 1 O, cis- 12-conjugated linoleic acid-paclitaxel （tl0, c12-CLA-PTX） on MCF-7 breast cancer cell line in vitro and in vivo. The in vitro cytotoxicity, apoptosis induction effect and cell cycle arresting effect of c9, t1 1-CLA-PTX and t10, c12-CLA-PTX were investigated. The in vitro cellular uptake of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX in MCF-7 cells were also analyzed. Besides, the anti-tumor activity of c9, tl 1-CLA-PTX and tl0, cl2-CLA-PTX was evaluated in MCF-7 tumor bearing nude mice in vivo. The in vitro cytotoxicity results showed that the value of ICs0 of the tl 0, c l2-CLA-PTX is （0.17±0.02） μM, compared with that of （1.08±0.15） μM in CLA-mixture-PTX and （6.50±1.20） μM in c9, tl 1-CLA-PTX treatment group （P〈0.01）. Both tl0, cl2-CLA-PTX and c9, t l 1-CLA-PTX increased the percentage of total apoptotic cells compared with that of control （P〈0.01）. And the rank of apoptosis induction efficacy was t 10, c 12-CLA-PTX〉CLA-mixture-PTX〉c9, t 11-CLA-PTX （P〈0.01）. Compared with untreated cells, the tl0, c12-CLA-PTX and c9, tl 1-CLA-PTX arrested cell cycle progression at the S and G2-M phase. The amount of cellular uptake of t 10, c 12-CLA-PTX was significantly higher than that of CLA-mixture-PTX （P〈0.01）, which was significantly higher than that of c9, t1 1-CLA-PTX （P〈0.01）. The rank of in vivo anti-tumor activity was tl0, c12-CLA-PTX〉CLA-mixture-PTX〉 c9, t1 1-CLA-PTX （P〈0.01）. In conclusion, our study demonstrated that both tl0, cl2-CLA-PTX and c9, tl 1-CLA-PTX has significant anti-tumor activity in MCF-7 cell line. And while c9, tl 1-CLA-PTX showed weaker inhibitory effect than CLA-mixture-PTX, str
The present study aimed to investigate the targeting effect of H7K（R2）2-modified pH -sensitive liposomes on U87-MG cells. Using coumarin-6 as a fluorescence probe, we prepared H7K（R2）2-modified p H-sensitive liposomes（designated as coumarin-6-PSL-H7K（R2）2）. The flow cytometry assay was used to evaluate the effect of H7K（R2）2 proportions on the cellular uptake and endocytosis pathways of coumarin--6--PSL--H7K（R2）2 on U87-MG cells. The circular dichroism（CD） spectroscopy assay was used to investigate the secondary structures of H7K（R2）2 peptide at pH 7.4 and H 6.8, respectively. Our results indicated that the 2.5% proportion of H7K（R2）2 in the coumarin-6--PSL-H7K（R2）2 was superior to those of 1% and 3.5% of H7K（R2）2. The uptake of coumarin--6-PSL--H7K（R2）2 on U87--MG cells was not inhibited by filipin, M-β--CD or chlorpromazine. The secondary structure of H7K（R2）2 at pH 6.8 was mostly presented as β--turn. In conclusion, we suggested that the appropriate proportion of H7K（R2）2 in the H7K（R2）2--modified pH--sensitive liposomes could be set at 2.5%. The cellular uptake pathway for H7K（R2）2-modified pH--sensitive liposomes was via the cell penetrating capacity of H7K（R2）2 which responded to acidic condition. The secondary structure of H7K（R2）2 at pH 6.8, which was presented as the shape of hairpin, might be mainly responsible for its targeting and cell penetrating effect.
In the present research, we selected Sylysia as a porous material and febuxostat（FBT） as model drug to prepare the FBT SiO2 solid dispersions using a solvent evaporation method. We firstly established an HPLC method for determining FBT in our prepared FBT SiO2 solid dispersions. And then, the characteristics of FBT SiO2 solid dispersions were investigated, including differential scanning calorimetry（DSC）, powder X-ray diffraction（PXRD）, scanning electron microscope（SEM）, particle size and distribution. The solubility and dissolution of FBT SiO2 solid dispersion were also evaluated. The results of DSC and PXRD showed that the FBT existed in an amorphous state in FBT SiO2 solid dispersions. The SEM and particle size results indicated that the shape and average particle size of FBT SiO2 solid dispersions was similar to the Sylysia. The solubility and dissolution of FBT in FBT SiO2 solid dispersions were significantly enhanced compared with the pure FBT. In conclusion, we successfully prepared FBT SiO2 solid dispersions to increase the solubility and dissolution rate of the poorly water-soluble FBT.
