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Objective@#To investigate the synergistic lethal effect and mechanism of arsenic trioxide (ATO) and aclacinomycin (ACM) on human acute myeloid leukemia cell line KG-1a.@*Methods@#Colony-forming assay was used to detect the proliferation of KG-1a cells treated with different concentration of ATO and ACM. Compusyn software was used to analyze the synergistic effect of ATO and ACM. Flow cytometry and Wright's staining were used to analyze the apoptotic rate of KG-1a cells induced by combined treatment of ATO and ACM. Western blot was used to determine the expression of proteins associated with apoptosis.@*Results@#The cytotoxicity of arsenic trioxide or aclacinomycin alone was in a dose-dependent manner. Flow cytometry analysis showed that the apoptotic rate of KG-1a cells treated with both 0.4 μmol/L ATO and 10 nmol/L ACM was (34.5±3.1)%, significantly higher than (7.6±1.1)% of 0.4 μmol/L ATO treatment or (18.7±2.3) % of 10 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 1.5 μmol/L ATO and 37.5 nmol/L ACM was (52.5±4.7)%, significantly higher than (19.1±3.2)% of 1.5 μmol/L ATO treatment or (27.7±2.2)% of 37.5 nmol/L ACM treatment alone (P<0.05). The apoptotic rate of KG-1a cells treated with both 3.0 μmol/L ATO and 75 nmol/L ACM was (61.3±4.5)%, significantly higher than (29.5±2.5)% of 3.0 μmol/L ATO treatment or (28.6±3.4) % of 75 nmol/L ACM treatment alone (P<0.05). In addition, the result of Wright's staining showed that combined treatment of ATO and ACM induced a more apparent phenotype of apoptosis when compared with single agent treatment. Compusyn software analysis showed that the combination index (CI) value of combined treatment group was less than 1, which indicated the synergistic effect of these two agents.@*Conclusions@#Combined treatment of ATO and ACM shows a synergistic lethal effect on human acute myeloid leukemia cell line KG-1a via activating the apoptotic pathway, which inhibits cell growth and induces apoptosis.
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Objective:To establish a test method for histamine-like substances in aclarubicin hydrochloride. Methods:According to the method in the appendix of Chinese Pharmacopoeia ( edition 2010 ) , the test of histamine-like substances was carried out. Re-sults:The test of histamine-like substances was not interfered by aclarubicin hydrochloride with the concentration below 0. 01 mg· ml-1 . Histamine-like substances in 4 batches of samples were determined by the established method, and the results were consistent with those of the test method for depressor substances. Conclusion: The test method for histamine-like substances is feasible with the limit of 1 μg·mg-1 .
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Objective To investigate the renoprective effect and its possible mechanism of Niaoduqing on the adriamycin(ADR)-induced nephropathy rats. Methods Forty eight male Sprague-Dawley rats were randomly divided into normal control(n=12), ADR-induced nephropathy(model, n = 12), Benazepril-treated ADR nephropathy(Benazepril, n=12)and Niaoduqing-treated ADR nephropathy(Niaoduqing, n =12)groups. The rat nephropathy model was established by adriamycin injection and unilateral nephrectomy. The rats were sacrifficed per batch at the 4th and 8th weekend.The pathological change of nephridial tissue, the 24-hour urinary protein excretion and renal function were examined. Immunohistochemistry was used to meassure the expression of fibronection(FN), collagenⅣ(COLⅣ), osteopontin(OPN). Results The 24-hour urinary protein excretion, BUN, Scr, triglyeride(TG), cholesterol(Cho)in model group were significantly higher than those in normal group(P<0.01), as well as more server glomerulosclerosis in kidney were observed in model group than those in control group(P<0.01), while the albumin(Alb)was lower (P<0.01). Compared with model group, the 24-hour urinary protein excretion, BUN, Scr, TG, Cho were significantly reduced and renal glomerulosclerosis was improved in Niaoduqing group(P< 0.01), while the Alb was higher(P<0.01). Conclusion Niaoduqing palys an important role in the prevention and treatment for nephropathy.
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Objective To evaluate the targeted killing of malignant melanoma cells by aclarubicin liposomes conjugated with vascular endothelial growth factor(ADM-VEGF-SSL)in vitro.Metheds To detect the binding abilitv of liposomes to malignant melanoma(MM)cells,the human malignant melanoma cell line A375 was cultured in the presence of ADM-VEGF-3H-SSL or ADM-3H-SSL for 2 days followed by the detection of radioactivity of these cells.Then.A375 cells were cultured with various concentrations(0.01,0.1,1,10,100 mol/L)of ADM-VEGF-SSL,ADM-SSL or free ADM for 48 hours in the 48-hour cytotoxity test,or for 0.5 hour followed by another 48-hour culture in drug-free medium in the 0.5-hour cytotoxity test.After that,MTT assay was used to detect the survival rate of these cells.Results ADM-VEGF-SSL could specifically bind to and kill A375 cells.The binding rate of ADM-VEGF-SSL was 2.15 folds as high as that of ADM-SSL.The survival rate of A375 cells after being treated with ADM-VEGF-SSL for 48 hour was similar to that with flee ADM(P＞0.05).but lower than that with ADM-SSL(P＜0.05),while the survival rate of melanocytes treated with ADM-VEGF-SSL was higher than that with free ADM or ADM-SSL(both P＜0.05).As shown by the 0.5-hour cytotoxity test.shortening the treatment course did not attenuate the effect of ADM-VEGF-SSL on A375 cells.Conclusions ADM-VEGF-SSL can specifically recognize A375 cells.efficiently deliver adriamycin into tumor cells,markedly inhibit the proliferation of A375 cells,and eventually,a targeted kill of these cells is realized.
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AIM: In order to evaluate the applicable value of LDL as a targeted vehicle for chemotherapeutic agents, we investigated and compared the inhibitory effects of LDL-ACM complex and free ACM on nude mice's subcutaneous implanted tumors derived from gastric cancer cell lines, SGC-7901 and NKM-45. METHODS: LDL-ACM complex was prepared and the tumor model of nude mice was established by subcutaneous implantation of SGC-7901 and NKM-45. Then, the groups of nude mice developed subcutaneous implanted tumors were received either LDL-ACM complex or free ACM. Subsequently, the tumor size, weight and leukemia cell counts were measured and the rates of tumor-inhibition and the survival were compared among the groups. RESULTS: The inhibitory effects of LDL-ACM complex on the tumors, especially on SGC-7901 implanted tumors were much more obvious than that of free ACM. It was also indicated that the action of LDL-ACM complex was mediated by LDL receptor. CONCLUSION: These results showed that LDL-ACM complex had significant inhibitory effects on the implanted tumors and the effect might be mediated by LDL receptor.