Anti-tumor Evaluation Of Salinomycin In Vitro And In Vivo

Objectivesâ‘ To observe the anti-proliferation effects of salinomycin on9human malignant cell lines in vitro and to analysis the anti-cancer spectrum of salinomycin.â‘¡Furthermore, a xenograft tumor model was used to investigate the inhibition effects ofsalinomycin on KCC853and HepG2tumor growth in vivo respectively.Methodsâ‘ MTT assay was performed to evaluate the growth inhibitory rate ofhuman cancer cell lines. Ranging from0.3125mg/ml to160mg/ml, cancer cells wasexplosed to a different dosage of salinomycin, paclitaxel for the positive control group.Measuring absorbance（OD Value） with a microplate reader, the half maximal inhibitoryconcentration(IC₅₀), the Max inhibition（Imax）, the growth curve of all kinds cells wereanalyzed by the ORIGIN8.0software.â‘¡Drug-sensitive cells, concentration of5×107per milliliter, were injected hypodermically into4-6weeks-old nude mouse. Tumorblock transplanting method was used to establishing the xenograft tumors model.Forty nude mice with basically the same tumor size were randomly divided into5groups.The way of drug delivery for the experimental group were intragastric administration.Paclitaxel was administered by vein injection. The weight of animals and the diameter ofthe xenograft tumors were surveyed every other day. At the end of the experiment, weexecuted the animals to collect the data. The growth inhibition rate was analyzed to evaluatethe anti-cancer activity of salinomycin.Resultsâ‘ The replicated MTT assay showed the potency window was covered bythe designed concentrations basically and the IC₅₀of salinomycin on each cell was about0.31ug/ml¹5.46ug/ml. All of the half inhibitory concentration was less than16ug/ml,while the Imax was about55.34%⁹9.35%. The results of curve-fitting were “S” curve model. The Imax of paclitaxel the fixed concentration（0.006ug/ml） was about13.5%⁷2.9%.â‘¡According to the observation of the KCC853xenograft tumors andHepG2xenograft tumors, the former experiment data showed that the inhibition ratio ofsalinomycin with the administer of10mg/ml,5mg/ml and2.5mg/ml were64.8%,60.7%and49.6%respectively, the latter experiment data showed that the inhibition ratio ofsalinomycin with the administer of20mg/ml,10mg/ml and5mg/ml were72.1%,57.9%and17.0%respectively. Compared with the control group, the tumor volume and tumorweight of three treatment group were significantly inhibited. There was positive correlationbetween the inhibition and the dose of salinomycin.Conclusionâ‘ Salinomycin can availably inhibit the growth of the9humanmalignant cell lines in a concentration-dependent manner.â‘¡Salinomycin can significantlyslow the growth of tumor xenografts in a dose-dependent manner in vivo.â‘¢According tothe appropriate dosing-schedules of salinomycin, there is no experimental animals died andno serious complications. All of those indicated that salinomycin is a compound, which isefficient and harmfulless in the setting of the measuring range.