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Objective To investigate the anti-cancer effect of CT-1042 on human gastric cancer cells SGC-7901 in vitro. Methods The inhibitory effect of CT-1042 on proliferation of SGC-7901 cells was evaluated by MTT method, Hoechst 33342 staining was performed to observe the influence of CT-1042 on cell apoptosis morphology. The cell apoptosis rate was detected by Annexin V and PI double dye. JC-1 probe was conducted to detect the CT-1042 effects on mitochondrial membrane potential. Flow cytometry was used to determine the cell cycle distribution. Results CT-1042 could significantly inhibit the proliferation of the subject cells, and induce the nuclear fragmentation, chromatin shrinkage. CT-1042 could induce subject cells mitochondrial membrane potential decreased, lead to cell apoptosis. CT-1042 could arrest the cycle progression of the subject cells in the G2/M phase. Conclusion CT-1042 has a significant inhibitory effect on human gastric cancer cell SGC-7901 in vitro, and the mechanism underlying may contribute to induce cell apoptosis and cycle arrest.
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Given the complexity of diseases and etiology of multiple targets and links,therapies with multi-drug combination towards multiple targets are better options for treating serious diseases,such as cancer,than a single-target medicine. Multi-drug combination may cause interactions at different levels,but the efficacy of these drugs manifests itself as synergism,addition or antagonism. Because there is no reliable quantitative method for synergism,addition and antagonism that can simultaneously withstand double test of mathematics and pharmacology,the development of novel drug combinations has come to a standstill. By exchanging the equivalent doses and introducing two basic principles that have been long neglected in the pharmacological field(the sequential principle for multi-drug use and the collective property of efficacy)into the geometrical analysis of the dose- effect relationships,the author has found the mathematical laws for the expected additive effect in multi-target drug combina?tion,and worked out a universal formula. The dose-effect relationship of the expected addition is a number set function of multi-drug combination doses with a closed interval,which performs as a belt in a two- dimensional coordinate,while the actual observed one presents as a curve. The number of curves that constitute the belt increases exponentially whith the incnease of combined drugs. By solv? ing the equation groups composed of the belt and the curve,related parameters in multi-drug combina?tion can be precisely calculated,such as dose ranges of synergism,addition and antagonism,as well as combination indexes based on dose and one based on efficacy,which will also provide a quantita?tive analysis method for interactions between various factors in biological systems.
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Objective To investigate the antitumor activity of the procaspase-3 activator SM-1 in BGC-823 cells in vivo and in vitro and the mechanisms.Methods The inhibitory effects of SM-1 on proliferation of BGC-823 cells were evaluated using MTT method, the cell apoptosis rate was detected by flow cytometry, and the expression of caspase-3 protein and procaspase-3 mRNA was detected by Western blotting and RT-PCR, respectively.SM-1 Antitumor activity was evaluated using the xenograft of BGC-823 cells in nude mice.Results SM-1 effectively inhibited the proliferation in vitro and in-duced apoptosis of BGC-823 cells in a dose-dependent manner.After treatment with SM-1 for 48 h, the protein expression levels of caspase-3 and mRNA expression levels of procaspase-3 were increased.SM-1 significantly inhibited growth of BGC-823 xenograft tumor at the 300 mg/kg dose and the inhibition rate was 56.3%(P<0.05).Conclusion SM-1 can significantly inhibit the tumor growth of BGC-823 cells in vivo and in vitro.The mechanism is possibly related to the activation of procaspase-3 and induced apoptosis of tumor cells.
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tuftsin,a physiologically active peptide,can promote phagocytosis,basically stimulates the macrophages or neutro-phils and improve their phagocytotic function.tuftsin can not di-rectly kill tumor cells.Due to its short structure and the charac-teristics of being susceptible to hydrolysis,it is difficult for tuft-sin to be made into medicine and applied clinically.However, derivatives of tuftsin-series and combination of tuftsin with other drugs can greatly enhance the cytotoxic effect on tumor cells of tuftsin.It has a broad prospect of research,especially deriva-tive-TP has a significant anti-tumor effect.Its mechanism is clear and its is expected to become a new type of anti-tumor bio-logical response regulator.
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Objective To establish a simple and useful kidney or bladder orthotopic tumor model used in preclinical pharmacodynamic evaluation.Methods Mouse model of orthotopic renal cancer were established by subrenal capsule implantation.After aspirating urine and irrigating bladder with PBS,the bladder urothelium was slightly impaired to establish the orthotopic bladder tumor model.Then, B-Ultrasound and H&E staining were used to confirm the availability.Results Tumors could be seen 2 weeks after surgery, accompanied by body mass loss of the mice.H&E staining showed that the tumor cells acted as infiltrative growth.The growth of tumor was inhibited by NTX in vivo, the tumor mass inhibitory rate of the KCC-853 orthotopic tumor model was 57.5% of 60 mg/kg NTX treatment and 48.8% in the T24 orthotopic tumor model of 30 mg/kg NTX treatment.Conclusion Our methods for establishing the orthotopic kidney or bladder tumor model are simple and practical.The results indicate that nitroxoline has potential antitumor activity.
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Aim To investigate the effect of TP on the expression of macrophages inflammatory protein ( MIP-1α) . Methods Total RNA of mouse Ana-1 cells and tumor associated macrophages were extracted, and MIP-1α mRNA was detected by RT-PCR. Mouse S180-xenografts were established by injecting S180 cells subcutaneously into the double abdominal flanks of the mice. The postoperative residual tumor models were generated in the right abdominal tumors when tumors grew into 250 mm3 . Animals were treated with TP or CTX, and tumor tissues were separated and MIP-1α was detected by immunohistochemistry. Results There was no significant difference of the expression of MIP-1α between Ana-1 cells and TAMs. TP couldn’ t affect MIP-1αexpression in Ana-1 cells while it signifi-cantly decrease MIP-1α expression in TAMs in a dose-dependent manner. TP significantly decreased MIP-1αexpression of tumor tissue compared with control group. Conclusions MIP-1α will be a new target of TP anti-cancer. Simple cell line tests in vitro couldn’ t reveal the real state in vivo.
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AIM: Antisense oligonucleotides against livin were designed with computer software. METHODS: Antisense oligonucleotides were designed according to the secondary structure of livin mRNA which was simulated with RNAdraw and Sfold. And then these oligonucleotides were transfected into Hela cells for inducing apoptosis. RESULTS: Five antisense oligonucleotides were designed using RNAdraw and Sfold, and effectively induced Hela cell apoptosis. CONCLUSION: The approach is effective and feasible to design antisense oligonucleotides by means of calculation with two kinds of software.
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Livin is a novel member of IAPs (inhibitors of apoptosis protein) family, which is expressed highly in a variety of tumors but not in majority of normal tissues. This protein contains a BIR domain and a RING finger domain just like other members of IAPs. It will be of great sigificance to investigate the relationship between Livin and tumors, and it might be a potential target for anti-cancer drugs.
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Apoptosis is involved in a variety of diseases. Cysteine aspartate specific protease (caspase), a protease family which executes apoptosis, plays a crucial role in course of apoptosis. It can be activated through various pathways. Some natural and synthetic caspase inhibitors will strengthen anti apoptotic action through inhibiting one or several caspase activity, and will become effective means in treating diseases caused by overapoptosis.
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Apoptosis is involved in a variety of physiological and path ol ogical conditions. Bax is proapoptotic member in signal pathway of apoptosis. It will contribute to the survival of cells if reducing its expression and activit y. Advances in factors influencing Bax, biological effects induce d by Bax knock-out, and antisense nucleotides targeted to Bax-mRNA were r eviewed in this article during recent years.
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Apoptosis is a cell suicide process with a major role in development and homeostasis in bodies. Dysregulation of apoptosis, involved with inhibitors of apoptosis (IAPs), contributes a variety of disease states including cancer. The recent progress of members of IAPs family and the anticancer strategy against IAPs is reviewed in this paper.
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Epidermal growth factor receptor (EGFR) tyrosine kinase is over-expressed in numerous human tumors, which plays pivotal roles in cellular signal transduction, and it is involved in a variety of tumor cellular behaviors such as proliferation, metastasis, angiogenesis and so on. Many investigations have indicated that tumor growth can be suppressed by inhibiting EGFR tyrosine kinase activity. Currently, several EGFR tyrosine kinase inhibitors are in clinical trial stage.
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Concern on antibiotics contamination has been raised because of its serious environmental impact in recent years.The application of antibiotics,measurement method for antibiotics,mechanism of antibiotics degradation,and impact of antibiotics contamination on environment and human health were reviewed and commented.The advisable solution and future researches were prospected in this review,too.