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Scientifically elucidating the mode of action of Chinese medicine has become an urgent challenge to Chinese medicine researchers.Opinions on the mode of Chinese medicine effect are active.The scientific hypothesis that additive effect is the key mode of action for Chinese medicine,trigger the scholars and experts in pharmacology field of Chinese medicine to think and contend.The opinion of additive effect provides a new interpretation for mode of action and action characteristics of Chinese medicine.It plays a positive role in the development of pharmacology of Chinese medicine.According to current research results of traditional Chinese medicine (TCM) and clinical cases,this paper made further thinking and summary on the key mode of action for Chinese medicine.The summary is as follows.The diversity of Chinese medicine structure and complexity of Chinese medicine targets determine the complicated mode of action of Chinese medicine.Mode of action for Chinese medicine is complex and variable,which is to adapt to changes in the environment.The genetic diversity of the body receptors due to evolution and the diversity of Chinese medicine and biological complex network control system have determined that a single component of Chinese medicine is more likely to act synergistically by targeting on different targets.From the point of view of Monarch,Minister,Assistant and Guide theory of Chinese medicine,additive effect has limitation.Therefore,just using additive effect is unable to fully explain the Chinese medicine compatible regularity of Monarch,Minister,Assistant and Guide theory.Additive effect is one of action types for Chinese medicine.It is worth to consider if there has any other more important action type for Chinese medicine.
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The elaboration of the mechanism and pharmacodynamic substance are the main obstacles to the modernization of Chinese medicine.The rich ingredient of Chinese medicine is almost attention,with a research strategy of forward pharmacology.This strategy often neglects the study of trace components of Chinese medicine.Synthetic lethality,a extremely complex gene interactions,is to magnify the effects of the co-regulation of biological effects (＞ 1 000 times).The theory of synthetic lethality has achieved good results in the development of anti-tumor drugs,including the discovery of PARP inhibitors,the clinical use of chemotherapy drug addition and attenuation combination.In view of this,this research model may be used to elucidate trace effective substance.Based on the reverse thinking of "targetcomponent-effect"and clear synergistic targets,the mechanism of traces and weak-potency substance of traditional Chinese medicine was studied,and the synergistic combination of potential was found.
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The interferons(IFNs) are a family of the multifunctional cytokines, which are a kind of highly active and multifunctional glycoproteins.Studies in recent years have shown that IFNs exert a powerful antitumor effect by regulating the proliferation of tumor cells, suppressing tumor metastasis and angiogenesis, and activating antitumor immune response.Combined with other tumor treatment methods, it can inhibit the development of a variety of blood system tumors and solid tumors.In addition, the use of IFNs inducers or IFNs combined with emerging immunotherapy can significantly increase the effectiveness of tumor therapy.This review focuses on our understanding of antitumor mechanism and clinical application of IFNs, and provides some guidance for future research and clinical treatment.
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Tumor metastasis is one of the important biological characteristics of malignant tumor,which is closely related with the prognosis of the cancer patients.High expression of ADAM8 in varieties of tumors was revealed in many recent studies,and such aberrant expression played a crucial role in regulating of tumor metastasis.Studies showed that overexpression of ADAM8 attenuated the intercellular adhesion effect,promoted tumor angiogenesis,and enhanced the degradation of ECM as well as the releasing of cytokines.Therefore,suppression of ADAM8 may lead to inhibition of tumor metastasis,which makes ADAM8 a particular attractive target as it can be used as a prognostic indicator and a potential therapeutic target of malignant tumor.A review about the relations between ADAM8 protein′s abnormal expression and tumor occurrence was discussed in this paper,also include discussion about the mechanisms of ADAM8 protein′s disorder-induced tumor formation,as well as therapeutic strategies based on ADAM8-targeted,which may provide references for follow-up research and clinical treatment.
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Multi-component Chinese medicine has been considered an important developmental direction for traditional Chinese medicine (TCM) formula.Nowadays,it is unfit to target a molecule for preventing or curing a disease because it resulted from multiple of factors and resulted in many indications.Thus,the idea focusing on the multiple targets for therapy is increasingly accepted by physicians and scientists.Here,we conceived a new simplified method for screening the active multi-component Chinese medicine based on the complexity of Chinese medicine,the multi-target property of protein signal transduction and the principle of Chinese medicine prescription.Combined with the traditional knowledge on tumor and latest antitumor research results of Chinese medicine and its compounds,the method was concretely illustrated.It helps us to transform the herbal compounds to new complex drugs targeting multiple signaling.
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Tumor necrosis factor receptor-associated protein 1 (TRAP1),as one of the main members of the heat shock protein 90 family, resists oxidative stress-induced apoptosis as well as predominantly maintains the integrity of mitochondria and cellu-lar homeostasis. Abnormal expression of TRAP1 was herein closely related to the onset and progression of a wide variety of tumors. As a key regulatory factor mediating energy metabolism within tumor cells, TRAP1 may be able to kill them by interfer-ing with such metabolism. More importantly, the abnormal ex-pression of TRAP1 played a less important role in normal cells, allowing TRAP1 to be a particularly attractive target as it can be used in tumor treatment or interference. The relationship be-tween abnormal expression of TRAP1 protein and tumor onset was reviewed. Besides, the mechanism by which disordered TRAP1 protein expression induced tumor formation was postula-ted, which may provide references for future research and clini-cal treatment.
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The study on tumor metabolism has been gradually be-come a hot spot in recent years .A lot of proteins involved in the regulation of tumor metabolism especially the glucose transporter protein 1(GLUT1).As a key regulatory factor mediating energy metabolism within tumor cells , GLUT1 can regulate the glucose intake and maintain the basic level of metabolism in tumor cells . More importantly, the abnormal expression of GLUT1 was asso-ciated with many kinds of tumors , of which GLUT1 was used to meet the energy requirement for the fast growth of tumor .Thus GLUT1 also played a crucial role in growth , differentiation and metastasis of tumor cells and prognosis of tumors .Meanwhile , as three-dimensional crystal structure of GLUT 1 was determined , it is possible to design the small molecular inhibitors of GLUT 1, which can realize “starve to death” tumor cells.GLUT1 can be a particularly attractive target for tumor treatment and interfer-ence.The relationship between abnormal expression of GLUT 1 protein and tumor metabolism was reviewed . Moreover , the mechanism of tumor metabolism regulated by GLUT 1 protein ex-pression and treatment of cancers were discussed , which may provide references for future research and clinical treatment .
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Aim To discuss the impact of important ac-tive ingredient of garlic diallyl sulfide———DATS on platelet activating factor (PAF ) mediated melanoma metastasis and its mechanisms.Methods ①MTT was used to test the effect of different concentrations of DATS on B16F10 and A375 melanoma cell growth number;②Scratch test and transwell were employed to test the effect of different concentrations of DATS on B16F10 and A375 melanoma cell migration;③ West-ern blot was used to test the effect of DATS on expres-sion of MMP-2,ERK,p38 induced by PFA;④Intrave-nous injection of tumor metastasis model was used to check the inhibition of DATS in PAF-mediated melano-ma metastasis.Results B16F10 cells relative growth rate fell to 73.21% and 48.78%,respectively,when DATS concentration reached 50 and 100 μmol·L-1 . DATS inhibited the levels of PAF-induced migration of melanoma cells B16F10 and vertical migration signifi-cantly,and inhibited B16F10 cells migration induced by PAF through inhibiting the expression of MMP-2, paxillin protein,FAK and other proteins.Conclusion DATS can significantly inhibit PAF-induced tumor metastasis, which is related to the inactivation of MAPKs.
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Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factor resulting in poor prognosis and leading to failure of treat-ment. In recent years, studies have shown that the extracellular matrix ( ECM) of tumor microenvironment plays a critical role in tumor metastasis. Tumor ECM fibrogenesis could form the cross-linked network structure, which not only provides nutrition and support to tumor, also it is necessary to tumor growth and inva-sion. These research results indicate that blocking ECM fibro-genesis may exert an inhibitory effect on tumor metastasis. Therefore, targeting ECM fibrogenesis has become a particularly attractive strategy as it can be used in the treatment of metasta-sis-related diseases. The ECM fibrogenesis in tumor is reviewed in this paper as well as the treatment strategies on tumor metas-tasis by targeting ECM fibrogenesis, which may provide refer-ences for follow-up research and clinical treatment.
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Tumor metastasis is one of the most important biologi-cal characteristics of malignant tumor, and it is also the main factors that cause treatment failure and poor prognosis. Clinical studies have shown that the number of platelets in patients with malignant tumor increased more significantly than that in benign tumor patients and healthy people, which indicate that platelet might be involved in the development process of tumor. Further study found that in the process of cancer spreading to blood, platelet could interact with tumor cells to form tumor emboli, helped tumor cells escape from immune surveillance, thus pro-moted the tumor metastasis. In recent years, related mechanisms on platelets in promoting tumor metastasis were revealed gradual-ly, and several targeted therapies based on platelets were also carried out. This paper reviews the role of platelet in mediating tumor metastasis by hematogenous spread and its mechanisms and discusses the therapy strategies that target platelet, which may provide references for follow-up research and clinical treat-ment.
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Aim To screen the potential inhibitors of post-transcriptional activity of pro-inflammatory media-tor TNF-α from the lipophilic constituents in Chinese Medicine Salvia miltiorrhiza Bunge ( Danshen) , we es-tablished dual luciferase reporter gene system pGL3-TNF-α3′UTR ( 3′untranslated region ) co-transfected with Renilla control gene. Methods Complementary DNA ( cDNA) template was obtained from human um-bilical vein endothelial cells ( HUVECs ) . The full length DNA of TNF-α 3′-UTR was amplified through PCR, and then connected the luciferase reporter vector pGL3-control after enzyme digestion. pGL3-TNF-α 3′UTR constructs were co-transfected with pSVRenilla into the mononuclear macrophages RAW264. 7 cells. The relative activity of reporter genes was measured by dual luciferase reporter ( DLR ) assay system after the stimulus of lipopolysaccharide ( LPS ) in presence or absence of tanshinones compounds. Results The pGL3-TNF-α3′UTR luciferase reporter gene was suc-cessfully constructed. The cloning DNA fragment and sequence were both consistent with the GENBANK da-tabase. LPS significantly induced the relative reporter activityof RAW264 . 7 cells transfected with pGL3-TNF-α 3′UTR. Among four tanshinones compounds, we found only cryptotanshinone could significantly de-crease LPS-induced relative reporter activity. Conclu-sion The pGL3-TNF-α 3′UTR construct combined with DLR assay system was successfully established, which can be used to discover the agents such as cryp-totanshinone that regulate the post-transcription of TNF-α in treatment of inflammatory and malignant dis-eases.
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MTH1 (MutT Homolog1 )as MutT homologous en-zyme,is a nucleotide pyrophosphatase,mainly involved in DNA damage repair process,especially plays an important role in the process of DNA replication in tumor cells.Recent studies have found that MTH1’s function is responsible for the development of a variety of tumors.Studies have shown that,MTH1 can remove tumor cells’oxidative DNA elements detrimental to the function-al structure,protecting tumor cell division and proliferation, maintaining tumor cell survival,however,normal cells do not need MTH1.Therefore,MTH1 may be only closely associated with abnormal cell growth.This makes MTH1 as therapeutic tar-gets that have been paid much attention.This article reviewed the relationship of MTH1 and tumor,discussed the mechanisms of MTH1 in tumor growth MTH1 and tumor treatment,so as to provide reference for clinical research and treatment of tumor.
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Objective To study the expressions of matrix metalloproteinase-1 3 (MMP-1 3)and p73 in gastric adenocarcinoma,and to explore the associations of the expressions of MMP-1 3 and p73 with the clinico-pathological features,and to evaluate their clinical significances for the prognosis of gastric adenocarcinoma metastasis.Methods The immunohistochemistry SP methods was used to evaluate the expressions of MMP-1 3 and p73 in 1 43 cases of gastric adenocarcinoma and 55 normal tissues adjacent to carcinoma,and their associa-tions to the clinicopathologic features were analyzed.Results The expression of MMP-1 3 in gastric adenocarci-noma was significantly higher than that in adjacent tissues of cancer (67.1 3% vs 1 6.35%),with a significant difference (χ2 =41 .1 0,P =0.000).The expression of p73 in gastric adenocarcinoma was significantly higher than that in adjacent tissues of cancer (58.74% vs 1 2.73%),with a significant difference (χ2 =33.86,P =0.000).In the gastric adenocarcinoma,the expression of MMP-1 3 was associated with peripheral lymph node metastasis (χ2 =1 1 .835,P =0.001 ),depth of invasion (χ2 =5.1 77,P =0.032)and TNM stage (χ2 =1 1 .1 07,P =0.001 ),but it was not correlated with the ages of patients (χ2 =0.1 1 3,P =0.853),tumor size (χ2 =0.338,P =0.591 )and tumor differentiation level (χ2 =3.628,P =0.072).In the gastric adenocarci-noma,the expression of p73 was associated with peripheral lymph node metastasis (χ2 =1 1 .440,P =0.001 ), tumor differentiation level (χ2 =5.407,P =0.025)and TNMstage (χ2 =9.497,P =0.003),but it was not correlated with the ages of patients (χ2 =1 .567,P =0.222),tumor size (χ2 =0.841 ,P =0.392)and depth of invasion (χ2 =0.554,P =0.498).The expression of MMP-1 3 was positively correlated with the expression of p73 in gastric adenocarcinoma group (r =0.684,P =0.000).Conclusion Both MMP-1 3 and p73 may participate in the development of gastric adenocarcinoma,which can be used as an important index for the eval-uation of invasiveness and metastasis in gastric adenocarcinoma.
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AngiotensinⅡ( AngⅡ) is the main functional bioac-tive peptide of the renin angiotensin system,and its basic function is to regulate salt-water homeostasis and blood pressure. Howev-er,recent studies have shown that AngⅡ plays a very important role in tumor formation and angiogenesis by acting on its type 1 receptor (AT1R) as a kind of potential growth factor. This arti-cle is a brief overview of the research on effects of AngⅡ-AT1R system in the process of tumor angiogenesis in recent years.
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As the major member of serine/threonine protein ki-nases family, glycogen synthase kinase 3β ( GSK-3β) has well characterized roles in the development of a variety of diseases. However, it is noticed that modulation of GSK-3β in tumor pro-gress is two-faced. Once the activity of GSK-3βas a“pro-onco-genic factor” is inhibited, opposing role as a“tumor suppressor”can also be disrupted, which will trigger the consequent side effect on activation of Wnt/β-catenin signaling pathway. The is-sue has placed a major obstacle to anti-GSK-3β in cancer treat-ment. In fact, functional compartmentalization of a large number of intracellular signaling events cross-talked with GSK-3β can prevent their mutual interference and determine the cell fate. Therefore, understanding the specific mechanisms of GSK-3β in regulation of diverse signaling systems or refinement of a sub-strate competitive inhibitor may have great significance to exploit approaches selectively target GSK-3β in tumor treatment.
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<p><b>OBJECTIVE</b>To study the molecular mechanism of anti-tumor effect of Danshensu (DSS) focusing on whether it is related to its antioxidation effect on redox state of non-small cell lung cancer A549 cells and relevant nuclear transcription factors and signal pathway.</p><p><b>METHOD</b>DPPH radical scavenging, ferric reducing, ferrous iron chelating assay and DCFH-DA fluorescence staining of ROS were introduced to detect antioxidant activity and ROS scavenging activity in vitro; MTf was adopted to analyze the effect of DSS on A549 cells viability at different time and dose. Western blot was used to detect the effect of DSS on the protein expression of hypoxiainducible factor HIF-1alpha and redox regulating transcription factor Nrf2 in A549 cells and the phosphorylation of upstream Akt, ERK1/2 MAPK.</p><p><b>RESULT</b>DSS could reduce the ROS level in A549 cells in a dose-dependent manner, which was related to it's strong DPPH radical scavenging activity. Moreover, DSS inhibited A549 cells proliferation in both dose- and time- dependent manner. Further study on molecular mechanism indicated that DSS suppressed redox regulator Nrf2, and down-regulated the phosphorylation of Akt and ERK1/2. However, DSS had no effect on HIF-la expression.</p><p><b>CONCLUSION</b>DSS might have the effect on treating non-small cell lung cancer by scavenging ROS and then inhibiting phosphorylation of Akt, ERK1/2 and down-regulating Nrf2 expression in A549 cells.</p>
Subject(s)
Humans , Carcinoma, Non-Small-Cell Lung , Metabolism , Cell Line, Tumor , Cell Proliferation , Drugs, Chinese Herbal , Pharmacology , Mitogen-Activated Protein Kinase 1 , Metabolism , Mitogen-Activated Protein Kinase 3 , Metabolism , NF-E2-Related Factor 2 , Metabolism , Oxidation-Reduction , Phosphorylation , Proto-Oncogene Proteins c-akt , Metabolism , Reactive Oxygen Species , Metabolism , Transcription Factors , MetabolismABSTRACT
<p><b>OBJECTIVE</b>To observe abnormal metabolic changes caused by ischemic cerebral apoplexy and the regulating action of Tongsaimai pellets on abnormal metabolism by analyzing the change of small molecules in plasma of ischemic cerebral apoplexy rat. To find the potential biomarkers, and to explore metabolic mechanisms of Tongsaimai pellets.</p><p><b>METHOD</b>Rat models of middle cerebral artery occlusion was established with electric coagulation, and rats were divided into 4 groups, model group, sham-operation group, Tongsaimai pellets group and positive control group. Tongsaimai pellets and positive control group were orally administrated by 13.2 g x kg(-1) x d(-1) of crude drugs and 32 mg x kg(-1) x d(-1) of Nimodipine respectively, m odel and sham-operation group by equal volume of distilled water for a week. Plasma of model and sham-operation group were collected, and plasma of Tongsaimai pellets and positive control group were collected on the 1st, 3rd , 7th day after administration. Endogenous metabolites of four groups were determined with GC-MS. Partial least squares discriminant analysis (PLS-DA) was applied to analyze multivariate data and set up model, and T-test was used in significant statistical analysis.</p><p><b>RESULT</b>Compared with sham-operation group rats, pyruvic acid, taurine and hydroxyproline obviously increased in model group rats, while lactic acid, glyceric acid, aminomalonic acid, fructose, tryptophan and leucine significantly decreased, so these metabolites were potential metabolic biomarkers. These endogenous metabolites except taurine got restoration in Tongsaimai group rats.</p><p><b>CONCLUSION</b>Abnormal metabolite level in plasma can be certainly recovered by Tongsaimai pellets, and the treatment of Tongsaimai pellets can be connected with the regulation of related metabolic pathways.</p>
Subject(s)
Animals , Male , Rats , Brain Ischemia , Blood , Drug Therapy , Drugs, Chinese Herbal , Therapeutic Uses , Fructose , Blood , Glyceric Acids , Blood , Hydroxyproline , Blood , Lactic Acid , Blood , Leucine , Blood , Malonates , Blood , Metabolomics , Methods , Pyruvic Acid , Blood , Rats, Sprague-Dawley , Stroke , Blood , Drug Therapy , Taurine , Blood , Tryptophan , BloodABSTRACT
<p><b>OBJECTIVE</b>To develop a spectral assay for determination of pachyman sulfate (PS) in rat plasma and to study the pharmacokinetics after intraperitoneal and intravenous administrations of PS.</p><p><b>METHOD</b>The spectral probe azur A (AA) was used to measure the concentration of PS in rat plasma, since AA could combine the sulfate groups in PS molecules and consequently induced the color change in solution. The optimal wavelengths, concentrations of plasma and AA in reaction system were determined by spectral scanning and serial tests. The plasma PS concentrations were measured at different time after intraperitoneal and intravenous administrations at the dosage of 60 and 20 mg x kg(-1), respectively.</p><p><b>RESULT</b>The optimal detecting wavelength was 620 nm. The maximum concentration of plasma and the optimal concentration of AA were 1.25% and 8.24 x 10(-5) mol x L(-1) in reaction system, respectively. The calibration curve was linear over the range of 0-10 mg x L(-1) with a correlation coefficiency of 0.995 9. The mean recovery was 100. 55%. The relative standard deviation (RSD) of intra-group and inter-group were all less than 5%. After intraperitoneal and intravenous administrations, the corresponding elimination half-lives were 319.09 min and 204.85 min, respectively. The elimination of PS in blood matched the open model of one compartment and first-order elimination. The bioavailability of PS via intraperitoneal injection was 69.12%.</p><p><b>CONCLUSION</b>The spectral probe AA was convenience, sensitive, accurate and steady to use for measuring the concentration of PS in the blood of rats; this made the research work of PS-pharmacokinetics easy and concise.</p>
Subject(s)
Animals , Male , Rats , Glucans , Blood , Pharmacokinetics , Infusions, Intravenous , Injections, Intraperitoneal , Poria , Chemistry , Rats, Sprague-Dawley , Spectrophotometry , MethodsABSTRACT
To observe clinical therapeutic effect of Ren Zhu Jian Wei Granules on precancerous lesion of stomach. Methods: 130 cases of precancerous lesion of stomach were randomly divided into tow groups, the treatment group (88 cases) treated with Ren Zhu Jian Wei capsules and the control group (42 cases) treated with Wei Fu Chun Tablets, and clinical data were analyzed. Results: The comprehensive therapeutic effect was 92. 0% in the treatment group and 73. 8% in the control group; and the clinical therapeutic effect was 94. 3% in the treatment group and 78. 6% in the control group with a significant difference (P
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AIM To observed the effect of procyanidins on DNA damage induced by carcinogen or hydroxyl radical (OH?),and inhibitory effect on topoisomerase. METHODS Using labeled TdR uptake assay and single cell gel electrophonesis. Topoisomerase was extracted from B16F10 cell lines, used agarose gel electrophoresis assay. RESULTS It was showed that hydroxyl radical (OH?) or different doses of MNNG can induce severe DNA damage of L 929 cell lines. Procyanidins can alleviate the damage induced by MNNG or OH?. It shows certain dose dependent effect relationship . But there is no significant inhibitory against Topo Ⅱ activity by procyanidins even at a dose of 50 ?mol?L -1 . CONCLUSION Procyanidins from grapes seeds can protect DNA damage,but not inhibit topoisomerase activity. This is one of cancer chemoprevention mechanism of Procyanidins.