Antitumor Effects of Ethanol Extract from Ventilago leiocarpa Benth on Sarcoma 180 Tumor-Bearing Mice and Possible Immune Mechanism / 中国结合医学杂志

OBJECTIVE@#To explore the antitumor effects of ethanol extract from Ventilago leiocarpa Benth (EEVLB) on sarcoma 180 (S180) tumor-bearing mice and the potential mechanism.@*METHODS@#Sixty mice were randomly assigned to 6 groups according to a random number table: normal group, model group, 5-fluorouracil (5-FU) group (0.02 g·kg@*RESULTS@#EEVLB with different concentrations achieved inhibition of tumor growth in vivo, wherein the high-dose group showed the most significant reduction in tumor weight and increased apoptosis of tumor cells (P<0.05). In addition, both net weight gain and spleen index of mice showed uptrend in EEVLB treatment groups (P<0.05). Besides, serum levels of IL-2 and IL-6, percentages of CD3@*CONCLUSIONS@#EEVLB exhibits promising antitumor activity in vivo. This effect might be due to activation of apoptotic signaling pathway, increase of cytokine levels and enhancement of immune function in tumor-bearing mice.

A polysaccharide fraction extracted from Pleurotus ostreatus mycelial biomass inhibit Sarcoma 180 tumor

ABSTRACT Fungi of Pleurotus genus have attracted a great interest due to their medicinal properties such as anti-inflammatory, antimicrobial and antitumor. These properties are attributed mainly to polysaccharides synthesized by Pleurotus. This work aimed to study the mycelial growth of P. ostreatus in submerged culture, evaluating the influence of the initial concentration of substrate (20 and 40 g/L of glucose) and the pH (4 and 6) on kinetic parameters of production of biomass. The effectiveness of different doses (10, 30 and 50 mg/kg) of a mycelium polysaccharide fraction extracted from P. ostreatus in reducing Sarcoma 180 development in mice was also verified. In the range of this study, maximum concentration of mycelial biomass (about 12.8 g/L) was obtained using 40.0 g/L of glucose, at pH 4.0. The total biomass productivity (Px) was not significantly affected by substrate concentration and pH, reaching values of 0.034 g/L.h. Sarcoma 180 tumor weight was reduced in 74.1, 75.5 and 53.7% when 10, 30 and 50 mg/kg were administered, respectively. These results show the high antitumor potential of intracellular polysaccharide fraction of mycelial biomass of P. ostreatus, particularly at lower doses of 10 and 30 mg/kg.

Comparison of therapeutic responses to an anticancer drug in three stocks of ICR mice derived from three different sources / 한국실험동물학회지

Korl:ICR mice, established by the Korean National Institute of Food and Drug Safety Evaluation (NIFDS), are characterized based on their genetic variation, response to gastric injury, and response to constipation inducers. To compare the inhibitory responses of ICR stocks obtained from three different sources to the anticancer drug cisplatin (Cis), alterations in tumor volume, histopathological structure, and toxicity were examined in Sarcoma 180 tumor-bearing Korl:ICR, A:ICR (USA source), and B:ICR (Japan source) mice treated with low and high concentrations of Cis (L-Cis and H-Cis, respectively). Tumor size and volume were lower in H-Cis-treated mice than in L-Cis-treated mice in all three ICR stocks with no significant differences among stocks. There was a significant enhancement of the necrotizing areas in the histological structures in the L-Cis- and H-Cis-treated groups relative to that in the untreated group. The necrotizing area changes were similar in the Sarcoma 180 tumor-bearing Korl:ICR, A:ICR, and B:ICR mice. However, there were stock-bases differences in the serum biomarkers for liver and kidney toxic effects. In particular, the levels of AST, ALT and BUN increased differently in the three H-Cis-treated ICR stocks, whereas the levels of ALP and CRE were constant. Taken together, the results of the present study indicate that Korl:ICR, A:ICR, and B:ICR mice have similar overall inhibitory responses following Cis treatment of Sarcoma 180-derived solid tumors, although there were some differences in the magnitude of the toxic effects in the three ICR stocks.

Indigofera suffruticosa Mill (Fabaceae): hepatic responses in mice bearing sarcoma 180 / Indigofera suffruticosa Mill (Fabaceae): respuestas hepáticas en ratones portadores de sarcoma 180

Indigofera suffruticosa is a plant generally used to treat infectious and inflammatory processes. This work aims to evaluate the histopathological changes in the liver tissue of mice with Sarcoma 180 after subchronic treatment with aqueous extract obtained by infusion and maceration of Indigofera suffruticosa leaves. Male mice were divided into four groups of six animals: G1, G2 and G3 patients with Sarcoma 180 and Sarcoma 180 G4 without sarcoma. G1 and G2 were treated with infusion mashing respectively (50 mg/kg ip); G3 and G4 controls received saline (15 ml/kg ip). The histopathological and morphometric analysis of liver tissue after subchronic treatment with aqueous extracts by infusion and maceration of the groups G1, G2 and G4 were similar and showed no degraded areas or leukocyte infiltration compared to G3, which shows a marked destruction of liver architecture. The results showed that after subchronic treatment with the aqueous extract of leaves Indigofera Suffruticosa obtained by infusion and maceration, the hepatic architecture was preserved, suggesting its use as an alternative hepatoprotective agent.

Indigofera suffruticosa es una planta utilizada para tratar procesos infecciosos e inflamatorios. Este trabajo tiene como objetivo evaluar los cambios histopatológicos en el tejido del hígado de ratones con sarcoma 180 después del tratamiento subcrónica con el extracto acuoso obtenido por infusión y maceración de las hojas de Indigofera suffruticosa. Los ratones machos fueron divididos en cuatro grupos de seis animales: pacientes G1 , G2 y G3 con Sarcoma 180 y G4 sin Sarcoma. G1 y G2 fueron tratados con infusión de maceración respectivamente (50mg/kg.ip); Controles G3 y G4 recibieron solución salina (15 ml/kg.ip). El análisis histopatológico y morfométrico de tejido hepático después de un tratamiento subcrónico con extractos acuosos por infusión y la maceración de los grupos G1, G2 y G4 fueron similares y no mostraron áreas degradadas o la infiltración de leucocitos en comparación a G3, que muestra una marcada destrucción de la arquitectura del hígado. Los resultados mostraron que después de un tratamiento subcrónico con el extracto acuoso de hojas de Indigofera suffruticosa obtenidos por infusión y la maceración, se conservó la arquitectura hepática, lo que sugiere su uso como una alternativa de agente hepatoprotector.

Co-delivery of paclitaxel and cyclosporine by a novel liposome-silica hybrid nano-carrier for anti-tumor therapy via oral route / 药学学报

In this study, we developed a novel liposome-silica hybrid nano-carrier for tumor combination therapy via oral route, using paclitaxel and cyclosporine as a model drug pair. Optimization of the preparation of the drug-loading formulation and characterization of its physicochemical parameters and drug release profile were performed in vitro. Then in vivo pharmacodynamics and pharmacokinetics studies were performed. The results showed that the obtained formulation has a small particle size (mean diameter of 100.2 +/- 15.2 nm), a homogeneous distribution [the polydispersity index was (0.251 +/- 0.018)] and high encapsulation efficiency (90.15 +/- 2.47) % and (80.64 +/- 3.52) % for paclitaxel and cyclosporine respectively with a mild and easy preparation process. A sequential drug release trend of cyclosporine prior to palictaxel was observed. The liposome-silica hybrid nano-carrier showed good biocompatibility in vivo and co-delivery of cyclosporine and paclitaxel significantly enhanced the oral absorption of paclitaxel with improved anti-tumor efficacy, suggesting a promising approach for multi-drug therapy against tumor and other serious diseases via oral route.

Anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes / 药学学报

The anti-tumor activity of folate receptor targeting docetaxel-loaded membrane-modified liposomes (FA-PDCT-L) was investigated in vitro and in vivo. FA-PDCT-L was prepared by organic solvent injection method. Transmission electron microscope, dynamic light scattering and electrophoretic light scattering were employed to study the physicochemical parameters of FA-PDCT-L. The inhibitory effects of docetaxel injection (DCT-I), non-modified DCT liposomes (DCT-L) and FA-PDCT-L on the growth of MCF-7 and A-549 cells at different incubation times were detected by CCK-8 assay; and the hemolytic test was employed in vitro. Tumor mice were randomized into 4 groups: DCT-I, DCT-L, FA-PDCT-L and control group (normal saline), and given drugs at 10 mg x kg(-1) x d(-1) through tail vein. The tumor volume, mice weight, inhibition rate of tumor and life span were measured at the end of experiments. The IC50 of the FA-PDCT-L for MCF-7 and A549 cell lines were significantly lower than that of DCT-I and DCT-L, without hemolysis reaction observed. Compared with control group, the weights of tumor in DCT-I, DCT-L and FA-PDCT-L were decreased, especially for FA-PDCT-L, with inhibitory rates at 79.03 % (P < 0.05). The life span and median survival time of FA-PDCT-L treated mice were significantly higher than that of DCT-I and DCT-L. In conclusion, FA-PDCT-L shows a good anti-tumor activity, indicating that it is potential carriers for DCT in the treatment of tumor.

Experimental study on inhibitory effect of GFW on transplantable tumor cell metastasis in S180 tumor-bearing mices / 中国中药杂志

<p><b>OBJECTIVE</b>To detect the effect of GFW on tumor cell metastasis in S180 tumor-bearing mice.</p><p><b>METHOD</b>S180 tumor-bearing mice model were replicated and divided randomly into 4 groups: the model group, the GFW group, the cyclophosphamide group and the combination administration group. VEGF in serum on each group was detected by ELISA, and the expression of metastasis suppressor gene nm23H1 and cell adhesion molecule CD44 in Sarcoma were detected by SABC immunohistochemical assay.</p><p><b>RESULT</b>Compared with the model group, the GFW group showed a significant decrease in VEGF in serum (P < 0.01). From their statistically significant difference, GFW was proved to promote the expression of metastasis suppressor gene nm23H1 and inhibit the expression of cell adhesion molecule CD44 (P < 0.05).</p><p><b>CONCLUSION</b>GFW has an effect on inhibiting tumor metastasis to some extent.</p>

Decreasing toxicity and synergistic effects of intracellular and extracellular polysaccharides from Phellinus igniarius to tumor-bearing mice / 中国中药杂志

To study the toxicity-decreasing and synergistic effect of intracellular and extracellular polysaccharides from Phellinus igniarius on S180 mice. The PIP and PIE were extracted from the products of liquid submerged fermentation of P. igniarius. Transplanting S180 mice tumor models were established so as to observe the changes in tumor inhibiting rate, indexes of the spleen and thymus, body weight, peripheral blood cells and IFN-gamma levels when CTX was used alone and when used in combination with the PIP and PIE from P. igniarius. The results indicate that the PIP and PIE from P. igniarius can increase the activity of body immunity, attenuate the toxicity of CTX as well, and improve the anti-tumor effects.

Effect of sphingosine-1-phosphate on chemotherapy-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the effects of sphingosine-1-phosphate (S1P) on cyclophosphamid (CTX) and cisplatin (DDP)-induced ovarian damage and on the efficacy of chemotherapy in mice bearing S180 murine sarcoma.</p><p><b>METHODS</b>Fifty-two female C57BL/6 mice were randomized into normal control group (n=10), tumor-bearing model group (n=14), CTX+DDP group (n=14), and S1P+CTX+DDP group (n=14). Before medication and on day 11 of medication during diestrus stage, the mice were sacrificed to measure the ovarian weight, numbers of primordial follicles and growing follicles, tumor weight, and serum levels of follicle-stimulating hormone (FSH), luteinizing hormone (LH) and estradiol ( E2).</p><p><b>RESULTS</b>At day 11 of medication, the levels of serum FSH and E2, but not LH, showed significant differences in CTX+DDP group from those in the other groups (P<0.01). FSH, E2, and LH levels were comparable between S1P+CTX+DDP group and the control group (P>0.05). The number of primodial follicles and weight of ovaries in CTX+DDP group decreased significantly compared to those in the other groups (P<0.01). The number of growing follicles in CTX+DDP group was significantly lower than that in the control and model groups(P<0.01), but similar to that in S1P group (P>0.05). The number of primodial follicles and growing follicles and ovarian weight in S1P+CTX+DDP group were close to those in the control and model groups (P>0.05). In CTX+DDP and S1P+CTX+DDP groups, the tumor weight were significantly lower than that in the other two groups (P<0.01), and the tumor inhibition rates were both higher than 60%.</p><p><b>CONCLUSION</b>S1P can ameliorate chemotherapy-induced ovarian damage in mice without affecting the efficacy of chemotherapy.</p>

Anticancer and Immunopotentiating Activities of Crude Polysaccharides from Pleurotus nebrodensis on Mouse Sarcoma 180

Pleurotus nebrodensis is an edible and commercially available mushroom in Korea. This study was conducted in order to evaluate the anticancer and immunopotentiating activities of crude polysaccharides, extracted in methanol, neutral saline, and hot water (hereafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of P. nebrodensis. beta-Glucan and protein contents in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. nebrodensis ranged from 23.79~36.63 g/100 g and 4.45~6.12 g/100 g, respectively. Crude polysaccharides were not cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at a range of 10~2,000 microg/mL. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 11.76~27.06% in mice previously inoculated with sarcoma 180. Treatment with Fr. NaCl resulted in an increase in the numbers of spleen cells by 1.49 fold at the concentration of 50 microg/mL, compared with control. Fr. HW improved the immuno-potentiating activity of B lymphocytes through an increase in alkaline phosphatase activity by 1.65 fold, compared with control at 200 microg/mL. Maximum production of nitric oxide (14.3 microM) was recorded in the Fr. NaCl fraction at 200 microg/mL. Production of tumor necrosis factor-alpha (TNF-alpha), interleukin-1beta (IL-1beta), and interleukin-6 (IL-6) was significantly higher, compared to control, and IL-6 production was highest, in contrast to TNF-alpha, IL-1beta, and positive control, concanavalin at the tested concentration of the various fractions. Results of the current study suggest that polysaccharides extracted from P. nebrodensis have a strong anticancer effect and may be useful as an ingredient of biopharmaceutical products for treatment of cancer.

Immunomodulating and Antitumor Activities of Panellus serotinus Polysaccharides

This study was initiated in order to investigate the anticancer and immunomodulating activities of crude polysaccharides extracted in methanol, neutral saline, and hot water (hereinafter referred to as Fr. MeOH, Fr. NaCl, and Fr. HW, respectively) from the fruiting bodies of Panellus serotinus. Content of beta-glucan and protein in Fr. MeOH, Fr. NaCl, and Fr. HW extracts of P. serotinus ranged from 22.92~28.52 g/100 g and 3.24~3.68 g/100 g, respectively. In vitro cytotoxicity tests, none of the various fractions of crude polysaccharides were cytotoxic against sarcoma 180, HT-29, NIH3T3, and RAW 264.7 cell lines at the tested concentration. Intraperitoneal injection with crude polysaccharides resulted in a life prolongation effect of 23.53~44.71% in mice previously inoculated with sarcoma 180. Treatment with Fr. HW resulted in an increase in the numbers of spleen cells by 1.3 fold at the concentration of 50 microg/mL compared with control. Treatment with Fr. NaCl resulted in improvement of the immuno-potentiating activity of B lymphocytes by increasing the alkaline phosphatase activity by 1.4 fold, compared with control, at the concentration of 200 microg/mL. Among the three fractions, maximum nitric oxide (13.48 microM) was recorded at 500 microg/mL in Fr. HW. Production of tumor necrosis factor alpha, interleukin-1beta, and interleukin-6 was significantly higher, compared to the positive control, concanavalin A, at the tested concentration. Therefore, treatment with crude polysaccharides extracted from the fruiting body of P. serotinus could result in improvement of antitumor activity.

Antitumor and Immunostimulating Activities of Elfvingia applanata Hot Water Extract on Sarcoma 180 Tumor-bearing ICR Mice

Elfvingia applanata, a medicinal mushroom belonging to Basidiomycota, has been used in the effort to cure cancers of the esophagus and stomach, and is also known to have inhibitory effects on hepatitis B virus infection. The hot water soluble fraction (as Fr. HW) was extracted from fruiting bodies of the mushroom. In vitro cytotoxicity tests showed that hot water extract was not cytotoxic against cancer cell lines such as Sarcoma 180, HT-29, HepG2, and TR at concentrations of 10~2,000 microg/mL. Intraperitoneal injection with Fr. HW resulted in a life prolongation effect of 45.2% in mice previously inoculated with Sarcoma 180. Treatment of Fr. HW resulted in a 2.53-fold increase in the numbers of murine spleen cells at a concentration of 50 microg/mL, compared with control. Incubation of murine spleen cells with Fr. HW at a concentration of 500 microg/mL resulted in improved immune-potwntiating activity of B lymphocytes through an 8.3-folds increase in alkaline phosphatase activity, compared with control. Fr. HW generated 12.5 microM of nitric oxide (NO) when cultured with RAW 264.7, a mouse macrophage cell line, at the concentration of 50 microg/mL, while lipopolysaccharide, a positive control, produced 15.2 microM of NO. Therefore, the results suggested that antitumor activities of Fr. HW from E. applanata might, in part, be due to host mediated immunostimulating activity.

Study on synergic and decreasing toxic effects of mineral water and Chinese herbal compound preparation on cisplatin / 中国中药杂志

<p><b>OBJECTIVE</b>The synergic and decreasing toxic effects of mineral water and Chinese herbal compound preparation (MWCHCP) on cisplatin were investigated in sarcoma 180 (S180) mice.</p><p><b>METHOD</b>The S180 mice were treated for 5 days with intraperitoneal injection of cisplatin(7.33 mg x kg(-1)) and oral administration of MWCHCP(1 925, 3 850, 7 700 mg x kg(-1)). Then the mice were killed and the tumor growth inhibition rate, organ index, diarrhea index were determined. Observe pathological sections of stomach to study the protective effect of MWCHCP. Reverse transcription-polymerase chain reaction (RT-PCR) was applied to investigate the tumour necrosis factor-alpha (TNF-alpha) expression level of the intestine.</p><p><b>RESULT</b>Combining with cisplatin and MWCHCP caused a tendency of increasing the tumor growth inhibition rate and significant attenution of cisplatin-induced diarrhea, visceral organ injury, gastric mucosal injury and decreased TNF-alpha mRNA level of intestine.</p><p><b>CONCLUSION</b>The present findings suggest that MWCHCP increases the inhibition rate of tumor growth of cisplatin and has a beneficial influence on gastrointestinal lesion induced by cisplatin.</p>

Pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone hydrochloride / 药学学报

This study is to compare the pharmacodynamics, pharmacokinetics and tissue distribution of liposomal mitoxantrone (Mit-lipo) and free mitoxantrone (Mit-free). The antineoplastic effect of Mit-lipo was evaluated on PC-3 human xenograft tumor model after repeated intravenous injection at dose levels of 1, 2 and 4 mg x kg(-1). The pharmacokinetic study of Mit-lipo and Mit-free was performed on dogs following a single intravenous injection. The tissue distribution of Mit-lipo and Mit-free was observed on S-180 bearing mice after a single intravenous injection. (1) Pharmacodynamics: Mit-lipo dose-dependently inhibited PC-3 tumor growth at a dose ranging from 1 to 4 mg x kg(-1). The antitumor effect studies showed that Mit-lipo significantly improved the therapeutic effect in comparison with free drug. (2) Pharmacokinetics: in comparison with Mit-free, the AUC and t(1/2) values of Mit-lipo at the same dose level were higher than those of Mit-free in Beagle dogs. The results showed that Mit-lipo had long circulation characteristics. (3) Tissue distribution in S-180 bearing mice: compared to Mit-free, Mit-lipo preferentially accumulated into tumor zones instead of normal tissues. Tumor AUC in Mit-lipo treated animals was 8.7 fold higher than that in mice treated with the same dose of Mit-free. The Cmax values of Mit-lipo in heart, kidney, lung, spleen and intestinal tissue in Mit-lipo were 30.2%, 161.6%, 20.2%, 27.9% and 78.3% lower than those of Mit-free, respectively. The pharmacokinetics and tissue distribution of Mit-lipo changed obviously, thus increasing therapeutic effect and improving drug therapeutic index.

Polysaccharides from Scurrula parasitica L. inhibit sarcoma S180 growth in mice / 中国中药杂志

To study the anti-tumor activity of Scurrula parasitica polysaccharides (SP). Water extraction and ethanol precipitation were used to isolate SP from S. parasitica leaf. S180, K562 and HL-60 cell lines proliferation inhibition by SP were detected by MTT assay. The expressions of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP+ SP could not inhibit cancer cell proliferation. SP ip could inhibit the growth of sarcoma S180 in mice, 100 mg x kg(-1) x d(-1). SP ip was the optimal dose on inhibiting S180 growth, with the tumor inhibition rate of 54%. The expression of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP. The result showed that SP could down-regulate the expression of Ki-67, CyclinD1 and Bcl-2 protein, and up-regulate the expression of Bax protein. It indicted that inhibiting cancer cell proliferation and promoting cancer cell apoptosis in vivo maybe one of the anti-cancer mechanisms of SP.

Synthesis of polyrotaxane-camptothecin conjugates and evaluation of its anti-tumor effect / 药学学报

To prepare polyrotaxane-camptothecin conjugates and evaluate its anti-tumor effect, polyrotaxane-camptothecin conjugates were successfully synthesized, and the release behavior was performed; MTT assay and cell morphology were used to examine the inhibition of cells' proliferation effect in vitro. The experimental study of the antitumor effect on S180 mice in vivo was also performed to further evaluate the anti-tumor effect of conjugate. The result showed polyrotaxane-camptothecin conjugates can effectively inhibit the proliferation in a dose dependent effect. In vivo study and cell morphology observation of S180 mice showed significant decrease in growth of tumor, degree of tumor infiltration and blood vessel number. The result indicated anti-tumor mechanism may be through affect the angiogenesis and reduced blood supply to tumor cells and then leading to necrosis.

Effect of sequential intratumoral injection of xenogeneic antigens for immunotherapy in immunized mice bearing S180 tumor / 南方医科大学学报

<p><b>OBJECTIVE</b>To investigate the therapeutic effect of sequential intratumoral injection of xenogeneic antigens in immunized tumor-bearing mice.</p><p><b>METHODS</b>Sequential intratumoral injection of the xenoantigens was performed in immunized mice bearing S180 tumor. The tumor size changes were observed, and the tumor-infiltrating lymphocytes (TIL) including CD3+CD4+T, CD3+CD8+T, and CD3+CD4+CD25+T lymphocytes were counted with flow cytometry. The concentrations of IL-2 and TNF-alpha in the tumor was measured using ELISA.</p><p><b>RESULTS</b>No significant difference was found in the number of CD3+T lymphocytes in the TILs between different groups. After the immunotherapy, the percentages of CD3+CD4+T, CD3+CD8+T and CD3+CD4+CD25+T lymphocytes were 54%, 22% and 2.91%, respectively, with the CD4+/CD8+ ratio of 2.49, significantly different from that in the control group (P<0.05). The concentrations of IL-2 and TNF-alpha were 100.61 pg/ml and 54.114 pg/ml, respectively, significantly different from those in the control group (P<0.05).</p><p><b>CONCLUSION</b>Sequential intratumoral injection of heteragenetic antigena can significantly increase the amount of effector cells and cytokines in the micro-environment of the tumor, and decrease the expression of T regulatory.</p>

Studies on the purification of water-soluble holothurian glycosides from Apostichopus japonicus and their tumor suppressing activity / 药学学报

To obtain water-soluble holothurian glycosides with high tumor suppressing activities from Apostichopus japonicus, macroporous resin, silica gel and gel-filtration column chromatograghy were used to purify the water-soluble holothurian glycosides, and their tumor suppressing activity and inducing apoptosis of tumor cells were examined in this study. The 70% ethanol fraction of macroporous resin column, the pSC-2 and pSC-3 fractions from silica gel column showed very strong tumor suppressing activity towards HeLa cells, A-549 lung cancer cells, SGC-7901 stomach cancer cells and Bel-7402 liver cancer cells. SC-2 and SC-3 fraction purified from Sephadex LH-20 gel-filtration column chromatography, with a purity above 99.6%, all had the properties of triterpenoid glycosides. Purified SC-2 fraction had remarkable tumor suppressing activity on HeLa cells in a dose- and time-dependent manner, and had prominent tumor suppressing activity to mouse S180 solid tumors in a dose-dependent manner. Besides, the SC-2 fraction also had remarkable ability in elevating mouse thymus index and spleen index. The purified SC-2 fraction could induce apoptosis of HeLa cells in a dose-dependent manner, and DNA fragmentation of HeLa cells occurred after treated 12 h with 10 mg x L(-1) and 50 mg x L(-1) of SC-2 fractions. From the results, it can be concluded that the purified SC-2 fraction of water-soluble holothurian glycosides has extremely strong tumor suppressing activity, and the suppression is realized by inducing tumor cells to undergo apoptosis. This study lays solid foundation for development of highly effective new natural anticancer agents from sea cucumbers.

PEGylated polyamidoamine dendrimer/methotrexate complex: pharmacokinetics and anti-tumor activity in normal and tumor-bearing rodents / 药学学报

Generation 4 polyamidoamine (PAMAM) dendrimer was PEGylated with polyethylene glycol (PEG) at an average molecular weight 5 000 via amide bond. PAMAM and PEGylated PAMAM (PAMAM-PEG) dendrimer were used as drug nanocarriers. Methotrexate (MTX), an antineoplastic agent, was selected as a model drug. PAMAM/MTX and PAMAM-PEG/MTX complexes were prepared. The pharmacokinetic characters and anti-tumor activity of the PAMAM-PEG/MTX complex were studied as compared with MTX injection and PAMAM/MTX complex by intravenous injection in rats and S180 tumor bearing mice, separately. The plasma samples from normal rats were analyzed by HPLC method, and concentration-time data were analyzed using a non-compartmental analysis. Their anti-tumor effects in vivo were evaluated against S180 solid tumors in mice by measuring average tumor weight and calculating the inhibitory rate of tumor on day 17 after successive injections. The results showed that both plasma half-life and mean retention time (MRT) of the complexes were longer than that of MTX injection (P<0.01), while the area under the plasma concentration vs time curve (AUC) of PAMAM-PEG/MTX was the largest as compared with that of free drug and PAMAM/MTX complex (P<0.01). The inhibitory rate of tumor of PAMAM-PEG/MTX complex enhanced 2.1 and 1.8 times over that of free drug and PAMAM/MTX complex, respectively, indicating that PAMAM-PEG/MTX exhibited the highest antitumor activity. In summary, PEGylated PAMAM could be useful as a potential drug delivery carrier.

The effect of focused ultrasound on the physicochemical properties of Sarcoma 180 cell membrane / 生物医学工程学杂志

This study was amied to detect the changes in the cell membrane of Sarcoma 180 (S180) cells induced by focused ultrasound and to probe the underlying mechanism. The viability of tumor cells was examined at various intensities and different treatment times by ultrasound at the frequency of 2.2MHz. Flow cytometry and fluorescence microscopy were used to detect the loading of fluorescein isothiocyanate dextran (FD500) which signifies the change of membrane permeability. The results showed that after the cells were treated by ultrasound, especially when irradiated for 60s, the number of fluorescent cell, which represented the transient change of membrane permeabilization with cell survival, increased significantly. Then the damage of cell membrane was evaluated by the measurement of lactate dehydrogenase (LDH) release which became more severe as the radiation time was increasing. The generation of lipid peroxidation was estimated using the Thibabituric Acid (TBA) method after irradiation. The results reveal that the instant cell damage effects induced by ultrasound may be related to the improved membrane lipid peroxidation levels post-treatment. The physicochemical properties of S180 cell membrane were changed by focused ultrasound. The findings also imply an exposure time-dependent pattern and suggest that the lipid peroxidation produced by acoustic cavitation may play important roles in these actions.