Effect and Mechanism of Cinobufotalin Against Gastrointestinal Malignant Tumors： A Review / 中国实验方剂学杂志

Digestive tract diseases， especially digestive tract tumors， including liver cancer， pancreatic cancer， and colorectal cancer， have high incidence in China. Digestive tract tumor is one of the top 10 cancers in terms of the number of new cases and deaths in the world， and the incidence and mortality of tumor diseases have been increasing year by year. Therefore， the prevention and treatment of tumors is particularly important. With the application and promotion of traditional Chinese medicine in the medical field and the rapid development of molecular biology and pharmacology， more and more potential active components of Chinese medicinal materials have been extracted and studied. These active components can inhibit tumor cells in a multi-target and multi-pathway manner. Cinobufotalin is an effective component extracted from the skin of Bufo bufo gargarizans. It has been prepared into a variety of agents with anti-tumor， immunomodulatory， cardiac boosting， pain-easing， anti-inflammatory， and swelling-relieving activities. In clinical practice， cinobufotalin is mainly used to assist the treatment of liver cancer， lung cancer， colorectal cancer， gastric cancer and other malignant tumors， which can reduce the adverse reactions of patients in the middle and late stages and improve the quality of life and five-year survival rate of patients. The available studies of molecular mechanism have demonstrated that cinobufotalin can play a therapeutic role by inducing cell apoptosis， regulating cell cycle， inhibiting cell proliferation and angiogenesis， modulating immune response， reversing multidrug resistance， enhancing radiochemotherapy sensitivity， inhibiting tumor inflammation， invasion， and metastasis， etc. This review focuses on the clinical application and mechanism of cinobufotalin against digestive tract tumors in recent years， aiming to provide a theoretical basis for the anti-tumor research of cinobufotalin， promote the application of cinobufotalin in tumor treatment， and facilitate the further research and development of this compound.

Research progress on the pharmacological effects and mechanisms of sanggenon C / 中国药房

Sanggenon C is a kind of flavonoid compound mainly extracted from the traditional Chinese medicine Morus alba. The pharmacological effects and mechanisms of sanggenon C are systematically reviewed and summarized， and it is found that this component can improve pulmonary fibrosis by regulating transforming growth factor-β1 and nuclear factor-κB； it can exert anti- tumor effects by inhibiting the proliferation of tumor cells and inducing the apoptosis of tumor cells； it can exert cardioprotective， neuroprotective and hepatoprotective effects by regulating multiple signaling pathways， such as calcineurin/nuclear factor of activated T cells 2， peroxisome proliferators-activated receptor α， and Ras homolog gene family member A/Rho-associated coiled- coil containing protein kinase， enhancing autophagy， reducing inflammatory response and reducing the level of oxidative stress； it can treat osteoporosis by inhibiting osteoclast uptake and promoting osteoblast formation； it has certain inhibitory effect on many enzymes； it can exert anti-inflammatory effects by regulating nuclear factor-κB signaling pathway； it can exert antioxidant effects by scavenging free radicals. However， researches on the pharmacological effects of sanggenon C mostly focus on the cellular and animal field， and the specific mechanism of action is not yet clear. In the future， basic research and clinical trials are still needed to explore and verify.

Pharmacological Activities， Pharmacokinetics， and Adverse Reactions of Polyphyllin Ⅱ： A Review / 中国实验方剂学杂志

As a rare Chinese medicinal material， Paridis Rhizoma is mainly distributed in Yunnan， Guangxi， and Guizhou in southwestern China， with the effect of clearing heat and detoxifying， alleviating edema and relieving pain， cooling liver and tranquilizing mind. It is particularly effective for injuries from falls， fractures， contusions and strains， snake bites， cold wind-induced convulsion， and other diseases， which has been used for more than 2 000 years. According to modern research， polyphyllin Ⅱ， one of the main active components of Paridis Rhizoma， belongs to diosgenin in structure. It has the anti-tumor， anti-inflammatory， antiviral， antibacterial， immune-regulating， antioxidant， and multidrug resistance-reversing activities， showing good application prospect. Especially， the anti-tumor effect of polyphyllin Ⅱ has attracted wide attention， and the mechanism is inhibiting proliferation， migration， and invasion of tumor cells， inducing cell cycle arrest， apoptosis， and autophagy， suppressing angiogenesis， and modulating tumor microenvironment. However， the pharmacokinetic results show that polyphyllin Ⅱ has low bioavailability in vivo due to the low solubility， poor absorption， unsatisfactory distribution， and slow metabolism， which limit the clinical application. In recent years， there has been an explosion of research on the adverse reactions of polyphyllin Ⅱ， such as the strong hemolytic activity and obvious cytotoxicity to liver， kidney， myocardium and cardiovascular cells. Thus， papers were retrieved from "CNKI"， "VIP"， "Wanfang Data"， "PubMed"， "Web of Science"， and "Elsevier SD" with "Paris saponin Ⅱ"， "Polyphyllin Ⅱ" as the main keywords， and the pharmacological activities and mechanisms， pharmacokinetics， and adverse reactions were summarized. The findings are expected to serve as a reference for the in-depth research， development， and utilization of polyphyllin Ⅱ.

Clinical antitumor application and pharmacological mechanisms of Dahuang Zhechong Pill / 中草药·英文版

Cancer still has elevated morbidity and mortality, which undoubtedly impacts the life quality of affected individuals. Remarkable advances have been made in cancer therapy, although the toxicities of traditional therapies remain an obvious challenge. Dahuang Zhechong Pill (DHZCP), developed by Zhongjing Zhang in the Synopsis of the Golden Chamber, represents an effective anticancer traditional Chinese medicine (TCM). In this review, it was found that DHZCP is therapeutically utilized in liver, lung, gastric, pancreatic and other cancers in clinic. Pharmacological evidence showed that its anti-tumor mechanisms mainly involve induced cell cycle arrest, apoptosis and autophagy, as well as suppressed tumor cell proliferation, obstructed angiogenesis and metastasis, enhanced immunity, and reversal of multidrug resistance. The present review provides a solid basis for the clinical application of DHZCP and may promote the wide use of TCM in clinical antitumor application.

Synergistic effect of Hsp90 inhibitor ginkgolic acids C15 ꞉1 combined with paclitaxel on nasopharyngeal carcinoma / 中南大学学报(医学版)

OBJECTIVES@#Nasopharyngeal cracinoma is a kind of head and neck malignant tumor with high incidence and high mortality. Due to the characteristics of local recurrence, distant metastasis, and drug resistance, the survival rate of patients after treatment is not high. Paclitaxel (PTX) is used as a chemotherapy drug in treating nasopharyngeal carcinoma, but nasopharyngeal carcinoma cells are easy to develop resistance to PTX. Inhibition of heat shock protein 90 (Hsp90) can overcome common signal redundancy and resistance in many cancers. This study aims to investigate the anti-tumor effect of ginkgolic acids C15꞉1 (C15:1) combined with PTX on nasopharyngeal carcinoma CNE-2Z cells and the mechanisms.@*METHODS@#This experiment was divided into a control group (without drug), a C15:1 group (10, 30, 50, 70 μmol/L), a PTX group (5, 10, 20, 40 nmol/L), and a combination group. CNE-2Z cells were treated with the corresponding drugs in each group. The proliferation of CNE-2Z cells was evaluated by methyl thiazolyl tetrazolium (MTT). Wound-healing assay and transwell chamber assay were used to determine the migration of CNE-2Z cells. Transwell chamber was applied to the impact of CNE-2Z cell invasion. Annexin V-FITC/PI staining was used to observe the effect on apoptosis of CNE-2Z cells. The changes of proteins involved in cell invasion, migration, and apoptosis after the combination of C15꞉1 and PTX treatment were analyzed by Western blotting.@*RESULTS@#Compared with the control group, the C15꞉1 group and the PTX group could inhibit the proliferation of CNE-2Z cells (all P<0.05). The cell survival rates of the C15꞉1 50 μmol/L combined with 5, 10, 20, or 40 nmol/L PTX group were lower than those of the single PTX group (all P<0.05), the combination index (CI) value was less than 1, suggesting that the combined treatment group had a synergistic effect. Compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the combination group significantly inhibited the invasion and migration of CNE-2Z cells (all P<0.05). The results of Western blotting demonstrated that the combination group could significantly down-regulate Hsp90 client protein matrix metalloproteinase (MMP)-2 and MMP-9. The results of double staining showed that compared with the 50 μmol/L C15꞉1 group and the 10 nmol/L PTX group, the apoptosis ratio of CNE-2Z cells in the combination group was higher (both P<0.05). The results of Western blotting suggested that the combination group could decrease the Hsp90 client proteins [Akt and B-cell lymphoma-2 (Bcl-2)] and increase the Bcl-2-associated X protein (Bax).@*CONCLUSIONS@#The combination of C15꞉1 and PTX has a synergistic effect which can inhibit cell proliferation, invasion, and migration, and induce cell apoptosis. This effect may be related to the inhibition of Hsp90 activity by C15꞉1.

Phototoxicity of Pheophorbide A Extracted from Gracilaria Lemaneiformis on Six Kinds of Cancer Cells / 肿瘤防治研究

Objective To investigate the photodynamic antitumor activity and chemical characteristics of pheophorbide A (PPBa)in vitro. Methods Breast cancer cells (MCF-7), lung cancer cells (A549), cervical cancer cells (HeLa), and three kinds of hepatoma cells (HepG2, hep3B and sk-Hep1) were planted in 96-well plates.The effects of light and dark toxicity, light intensity, and drug concentration on the phototoxicity of PPBa were investigated by MTT, and the uptake of PPBa was observed by Hoechst staining under a confocal microscope.The production of singlet oxygen was observed by flow cytometry and confocal microscopy with the reactive oxygen species detection kit.The photobleaching of PPBa was investigated by measuring the absorbance by a microplate reader according to the luminescence characteristics of PPBa. Results PPBa showed strong phototoxicity and low dark toxicity to six kinds of cancer cells, and IC50 values to cancer cells were as follows: MCF-7:1.033 μmol/L, A549:1.911 μmol/L, HeLa: 2.319 μmol/L, HepG2:2.015 μmol/L, Hep3B: 2.089 μmol/L, sk-Hep1:2.467 μmol/L.The main uptake site of PPBa was the cytoplasm.The production of singlet oxygen was strongly dependent on the administration concentration, and photobleaching was very low. Conclusion For the six kinds of cancer cells, PPBa has the highest phototoxicity to breast cancer cells (MCF-7), with excellent properties and ideal photosensitizer characteristics.

Anti-tumor Effect and Mechanisms of Triterpenoids and Polysaccharides in Ganoderma lucidum： A Review / 中国实验方剂学杂志

With the population aging， the morbidity and mortality of cancer patients continue to rise. At present， the treatment methods for tumors include surgery， chemotherapy， radiotherapy， targeted therapy， and immunotherapy. However， most chemotherapeutic drugs can cause severe side effects and drug resistance. Therefore， as an alternative therapy， traditional Chinese medicine （TCM） treatment can effectively relieve the clinical symptoms of tumor patients， improve the quality of life， inhibit or stabilize the development of tumors， and prolong the survival period of patients. Due to the good safety of Chinese medicine， its potential anti-cancer activity has attracted increasing attention. Ganoderma lucidum， a treasure of Chinese medicinal material， is a medicinal fungus with a history of more than 2 000 years in China. So far， many studies have proposed the anti-cancer properties of G. lucidum. G. lucidum has extensive pharmacological activities， such as anti-tumor， anti-atherosclerosis， and anti-aging. It can also regulate immunity， protect the liver and the heart， and reduce blood glucose and lipid. The chemical composition of G. lucidum is complex. At present， it is proved to contain polysaccharides， triterpenoids， alkaloids， nucleosides， amino acids， and various trace elements. The anti-tumor mechanisms of polysaccharides and triterpenoids in G. lucidum are mainly achieved by apoptosis induction， immune regulation， anti-angiogenesis， and induction of cell cycle arrest. Currently， it has been widely used in the adjuvant treatment of complex tumors such as lung cancer， liver cancer， cervical cancer， prostate cancer， breast cancer， and colon cancer. The present study reviewed the bioactivities and mechanisms of triterpenoids and polysaccharides in G. lucidum in recent years and highlighted the anti-tumor effects and mechanisms to provide references for the further development and utilization of G. lucidum.

Anti-tumor Effect of Chinese Herbal Polysaccharides： A Review / 中国实验方剂学杂志

Tumor has become one of the major diseases threatening human health at present. Conventional therapies for tumor have serious side effects and are prone to drug resistance， while new therapies are expensive and impose a heavy burden on patients. Chinese herbs effective in the treatment of tumor contain a variety of natural active ingredients， and many anti-tumor drugs used in clinical practice are derived from Chinese herbs. Polysaccharides， ubiquitous in Chinese herbs， are easy to extract and have antitumor， antiviral， and antioxidant activities. Studies have demonstrated that the polysaccharides from Chinese herbs have significant anti-tumor effect and are characterized by multi-target and multi-mechanism functioning， which can avoid the development of drug resistance， exhibiting a great research value and the potential to be developed into novel anti-tumor drugs. Their anti-tumor mechanisms mainly include the inhibition of tumor proliferation， promotion of apoptosis， induction of autophagy， influence on cell cycle， inhibition of tumor angiogenesis， modulation of epithelial-mesenchymal transition （EMT） and immunity， promotion of tumor oxidative stress， and regulation of phosphatidylinositol 3-kinase/ protein kinase B （PI3K/Akt）， Toll-like receptor 4 （TLR4）， mitogen-activated protein kinase/nuclear factor-kappa B （MAPK/NF-κB）， adenosine 5'-monophosphate （AMP）-activated protein kinase/mechanistic target of rapamycin （AMPK/mTOR）， epidermal growth factor receptor/extracellular signal-regulated kinase （EGFR/ERK）， p53， and Wnt/β-catenin signaling pathways.

Antitumor and Complementary Effects of Original Konjac Jelly Mixed with Soymilk, Cheese and Vitamin C for Cisplatin-resistant Bladder Cancer / 日本補完代替医療学会誌

In this study, we aimed to develop foods with antitumor and complementary effects against cisplatin (CDDP)-resistant bladder cancer. UMUC3, a human bladder cancer cell line was exposed to CDDP and cultured over a prolonged period to prepare UMUC3-CR, a CDDP-resistant subline. Androgen receptor mRNA expression was high in the UMUC3-CR subline. Genistein and vitamin C suppressed UMUC3-CR tumor growth. Additionally, the liberal intake of cheese in parental cell UMUC3-transplanted mice was associated with prolonged survival. Therefore, we created konjac jelly (KIK300) containing soy milk, cheese, and vitamin C as the main ingredients. Liberal administration of KIK300 to UMUC3-CR-transplanted mice suppressed tumor growth and reduced vascular endothelial growth factor mRNA expression. Furthermore, we observed no weight loss in the animals, their skin condition improved, and exercise capacity was improved. In conclusion, this study suggests that KIK300 may show antitumor and complementary effects on CDDP-resistant bladder cancer.

Preparation of Chelerythrine Nanoparticles and Evaluation of Anti-melanoma Activity in vitro / 中国药房

OBJECTIVE：To prepare chelerythrine nanoparticles（CHE-NPs），optimize their formulation ，and evaluate its drug release behavior in vitro and its inhibitory effect on melanoma. METHODS ：Using methoxy polyethylene glycol-poly （lactic-co- glycolic acid ）（mPEG-PLGA）as carrier ，CHE-NPs were prepared by the nano-precipitation method. HPLC method and dialysis bag method were used to determine entrapment efficiency and drug loading. The formulation of CHE-NPs was optimized by Box-Behnken response surface design using overall desirability （OD）of them as dependent variables ，CHE dosage ，mPEG-PLGA concentration and poloxamer 188（F68）concentration as independent variables. The particle size and Zeta potential of CHE-NPs prepared by the optimal formulation were detected ；the characteristics of drug release in vitro were investigated ；the effects of CHE and CHE-NPs on survival rate of mice B 16 melanoma cells were compared ，and median inhibition concentrations （IC50）of them were calculated. RESULTS ：The optimal formulation included CHE of 2 mg，mPEG-PLGA of 13 mg/mL，F68 of 1.8％. Average entrapment efficiency rate of CHE-NPs prepared by the optimal formulation was （80.18±1.11）％，average drug loading was （11.36±0.28）％，average OD value was 0.96±0.04 [the relative deviation from predicted value （0.90）of OD was 6.67％]； particle size was （113.1±1.40）nm，and Zeta potential was （－21.6±0.29）mV；polydispersity index was 0.07±0.01（n＝3）； accumulative release rates of CHE control and CHE-NPs were 90.87％ and 68.68％ within 8 h，and drug release behavior in vitro of the latter was in accordance with Weibull kinetic model. Inhibitory effect of CHE-NPs on B 16 melanoma cells was significantly stronger than that of CHE ；the 24 h IC 50 of CHE-NPs and CHEwere 69.35 and 107.36 μg/mL，respectively. CONCLUSIONS ：The prepared CHE-NPs show good sustained-effect and high capacity of drug loading ，and strengthen the inhibitory effect of CHE on melanoma.

Daphnane-type diterpenes from genus Daphne and their anti-tumor activity / 中草药·英文版

Daphnane-type diterpenenoids are the major biologically active constituents in the genus Daphne. We find that there are about 101 Daphnane-type diterpenes in this genus, most of those compounds show different degrees of inhibitory effect on various cancer cell. Some of them have been studied in depth and the potent molecular mechanisms might be associated with modulation of different cell-signaling pathways. In addition, some compounds of this type also can inhibit the synthesis of protein and DNA. Absolutely, the anti-tumor activity of Daphnane-type diterpenes is worthy of attention. Unfortunately, most of the current research on the activity of these compounds is focused on simple drug efficacy, and its in-depth mechanism research is far from enough. On the other point of view, there still exists wide growing space on the depth of these compounds.

Symptom Relief and Anti-tumor Effects of Glucocorticoids Enable Terminal Lymphoid Malignancy Patients to Receive Outpatient Treatment at Home

Glucocorticoids are one of the key drugs used in palliative therapy. They have several palliative effects. However, aside from these effects, glucocorticoids have anti-tumor effects on lymphoid malignancies. In particular, for patients with lymphoid malignancy in the terminal stage of the disease, this medical modality can produce both symptomatic relief and anti-tumor effects without serious side effects. This article presents two impressive cases of patients with terminal lymphoid malignancy treated with glucocorticoids, who showed survival advantages and improved quality of life.

Anti-tumor Activity and Survival Impact of Whole Adlay Hot Water Extract in Sarcoma Mouse Model / 日本補完代替医療学会誌

Background: Adlay (Coix lacryma-jobi L. var. ma-yuen Stapf) has been used both in traditional Chinese medicine and as a nourishing food based on its unique biological effects and highly nutritional values. In the present study, we investigated the anti-tumor effect of a hot-water adlay extract in sarcoma mice model. Materials and Methods: The hot water extract of whole adlay was orally administered to mice for one week, after which Sarcoma-180 cells (1×106) were subcutaneously implanted into the abdomen. Thereafter, the tumor growth was monitored and mouse survival was examined. Results: Tumor weights measured at 18 days were significantly lower in mice treated with extract (100 and 300 mg/kg/day) than those in control group (p<0.01). Moreover, mice treated with extract (100 mg/kg/day) showed apparently longer survival than control group evaluated until 32 days (p<0.05). Conclusion: These findings indicate that hot water adlay extract appears to have some anti-tumor effects in vivo insarcoma cells.

Synthesis，Characterization and Anti-tumor Effect Evaluation of Novel Ampelopsin Derivative Poly （γ-glutamic Acid）-ampelopsin Conjugate / 中国药房

OBJECTIVE：To desig n and sy nthesize poly （γ-glutamic acid ）-ampelopsin（γ-PGA-AMP），and to characterize it and evaluate its anti-tumor activity in vitro . METHODS ：Synthetic product was produced through an esterification reaction between γ-PGA and ampelopsin. The structure of synthetic product was characterized by the UV spectrophotometry ，Fourier transform infrared（FT-IR）spectroscopy，1H-NMR spectra and the quantitative elemental analysis. The content of ampelopsin in synthetic product was determined by UV absorption spectrometry at 292 nm. Using 5-FU as positive control ，MTT assay was used to determine inhibitory effects of γ-PGA-AMP and ampelopsin on human breast cancer cell MCF- 7，human liver cancer cell HepG 2 and human lung cancer cell A 549. The IC 50 was calculated. RESULTS ：The results showed that the free 7-hydroxyl group of ampelopsin and the a-carboxyl group of γ-polyglutamic acid had been esterified to obtain γ-PGA-AMP；the yield of γ-PGA-AMP was 55.7％，and the content of ampelopsin was 32.3％. The inhibitory effect of γ-PGA-AMP and ampelopsin on MCF- 7，HepG2 and A 549 cells was obvious. IC 50 of γ-PGA-AMP（to 3 above tumor cells ）were 40.19，28.29 and 55.23 μg/mL，those of ampelopsin were 105.30，81.23，130.10 μg/mL，those of 5-FU were 24.72，87.98，30.99 μg/mL，respectively. CONCLUSIONS ：γ-PGA-AMP with anti-tumor effect in vitro is synthesized successfully ，and its anti-tumor effect is stronger than that of ampelopsin.

Synergistic anti-tumor effect of metformin and dichloroacetate in MFCW-ampIified neuroblastoma BE-2C cells / 中国药理学通报

To investigate the effect of metformin production of combined group compared with alone combined with dichloroacetate on the proliferation of A/FC/V-amplified neuroblastoma BE-2C cells and its mechanisms. Methods The inhibitory effects of metformin and dichloroacetate alone or in combination on BE-2C cells was measured by CCK-8 assay; the concentrations of glucose and lactic acid in the medium were measured by a glucose test kit and L-lactic acid assay kit; cell apoptosis was determined by flow cytometry (FCM) with Annexin V-FITC conjugated propidium iodide (PI) staining; the expressions of apoptosis related protein were detected by Western blot. Results Metformin and dichloroacetate showed significant proliferation inhibition activity on BE-2C cells; there was obviously decreased glucose uptake and lactic acid production of combined group compared with alone group (P <0. 01) ; the apoptotic rate was significantly higher in combined group compared with that in alone group (P <0. 01) ; Bax and cleaved caspasce-3 protein expression markedly increased in combined group, but Bcl-2 protein expression significantly increased compared with alone group (P <0. 01). Conclusions Metformin combined with dichloroacetate shows a significant synergistic anti-tumor effect against BE-2C cells by reducing the accumulation of lactic acid caused by metformin and inducing apoptosis.

Review on Anti-tumor Effects Mechanism and Clinical Application of Agrimonia pilosa / 世界科学技术-中医药现代化

Agrimonia pilosa is one of the traditional Chinese herbal medicines for 2000 years history. Due to its various pharmacological effects, it is widely used in the clinical treatment of tumors and other diseases. Presently malignancy has become an important factor threatening human health that the anti-tumor effect of Agrimonia pilosa has attracted great attention. The author reviewed its anti-tumor effect mechanism by articles arrangement of experimental study, clinical study and experience introduction. A series of study revealed 3 mechanisms: blocking cell cycle, inducing apoptosis and strengthening the cellular immunity. As a kind of traditional Chinese herbal medicine which has anti-tumor effect, the Agrimonia pilosa should be reasonably applied according to the related research and previous experience.

Establishment of the culture system of γδ T cells in vitro and the anti-tumor effect / 中华肿瘤杂志

Objective@#To establish the culture technique for culturing γδ T cells in vitro and evaluate the basic characteristics, security and anti-tumor effect of the cultured γδ T cells.@*Methods@#Phytohemagglutinin, zoledronic acid, interleukin-2 and interleukin -7 were used to induce the abundant expansion of peripheral blood mononuclear cells in vitro. Flow cytometry assay, in vitro killing assay and mouse model of human lung cancer were also adopted to assess the characteristics and the anti-tumor effect of cultured γδ T cells. Additionally, the contamination of exogenous agents and the acute toxicity of γδ T cells were determined.@*Results@#After culturing 14-16 days in vitro, the total number of γδ T cells was more than 1.0×1010. Among these γδ T cells, CD3+ γδ TCR+ cells accounted for more than 90%. None of contaminations of bacteria, fungi, mycoplasma and virus were observed. At effect target ratio (E/T ratio) of 50/1, killing efficiency of γδ T cells cultured in vitro to SK-MES-1, Ho8910, A549 and K562 reached more than 65%. In vivo experiments showed that the tumor volume of γδ T-treated mice was (828.99±61.05) mm3, significantly lower than (1 723.51±84.30) mm3 of the control mice (P<0.05). Meanwhile, no acute toxicity effect was observed in γδ T cells treated mice.@*Conclusion@#The number, purity and activity of γδT cells cultured in our institute can reach the requirement of clinical application, and the γδT cells also display strong cytotoxic activity against tumor cells such as lung cancer, ovarian cancer and leukemia.

Construction of mouse IL-33-armed recombinant oncolytic virus and its synergistic inhibitory effects on tumor / 中华微生物学和免疫学杂志

Objective To construct a recombinant oncolytic virus vvmIL33 that can steadily se-crete mouse IL-33 protein (mIL-33) in targeted tumor cells and to study its synergistic inhibitory effect on tumor. Methods Mouse IL-33 gene sequence was amplified by PCR and inserted into the eukaryotic ex-pression vector pCMS1. The constructed pCMS1-mIL33 was transfected into the parent virus (vJS6)-infected cells by Lipofactamine. Recombinant oncolytic virus vvmIL33 was purified by cell flow sorting. Enzyme-linked immunosorbent assay ( ELISA) was used to detect the level of mIL-33 protein in the culture superna-tant of vvmIL33-infected tumor cells. Recombinant oncolytic virus vvmIL33 and parental virus vJS6 were re-spectively used to infect tumor cells, and then analyzed by plaque formation assay and MTS kit. T cell co-culture experiments were performed to examine the anti-tumor ability of T cells induced by vvmIL33-infected tumor cells. Results Electrophoresis results of the recombinant plasmid pCMS1-mIL33 showed that mIL-33 gene was inserted successfully. Compared with the control group, vvmIL33 could steadily secrete high levels of mIL-33 protein in MC38 cells after infection (P<0. 001). Results of the plaque formation assay showed that vvmIL33-or vJS6-infected CV1 and MC38 cells produced similar amounts of virus at various time points without statistical difference (P>0. 05). Under different multiplicity of infection (MOI), the lytic ability of vvmIL33 against tumor cells was similar to that of vJS6 without statistical difference (P>0. 05). In the T cell co-culture experiments, the concentration of INF-γ protein produced by T cells in the vvmIL33-infected MC38 cell group was significantly increased as compared with that of the vJS6 group (P<0. 05). Moreover, the cytotoxic effect of induced T cells on tumor cells was also significantly increased (P<0. 05). Conclusion The recombinant oncolytic virus vvmIL33 was successfully constructed without damaging its ability to repli-cate and induce tumor cell lysis. Oncolytic virus carrying mIL-33 enhanced the immune effect of T cells and increased anti-tumor effect.

Preparation and antitumor effects of tanshinone ⅡA loaded albumin nanoparticles / 中国中药杂志

In this study, the tanshinone ⅡA loaded albumin nanoparticles were prepared by high pressure homogenization method. The formulation was optimized by central composite design-response surface method (CCD-RSM), with the particle size, encapsulation efficiency, and drug loading as indexes to investigate their in vitro anti-tumor effect. The results showed that the prepared nanoparticles had uniformly spherical morphology and uniform particle size distribution. The average particle size, encapsulation efficiency and drug loading of nanoparticles were about (175.7± 3.07) nm, 90.8%±1.47% and 5.52%±0.09%, respectively. Tanshinone ⅡA loaded albumin nanoparticles showed a more powerful antitumor effect than free tanshinone ⅡA for human promyelocytic leukemia NB4 cells. The preparation method of the drug-loaded albumin nanoparticles was simple and easy, and can significantly improve the solubility of tanshinone ⅡA, so it was helpful to extend its application in therapies against hematological malignancies.

Distribution in the body of targeted ursolic acid liposomes and their inhibitory effect on mice transplanted tumor / 中国药学杂志

OBJECTIVE: To study the distribution of folate receptor targeted ursolic acid liposomes and evaluate its antitumor effects on human epidermoid carcinoma xenografts in nude mice. METHODS: Folate derivative was used as targeting molecule and conjugated with mPEG-DSPE for obtaining liposome with long circulation features. This novel targeted agent was prepared by a thin-film dispersion method and ursolic acid was loaded into the liposomes as the anticancer drugs. Tissue distribution of liposomes in heart, liver, spleen, stomach, kidney and tumor were investigated. The antitumor effect of the targeted ursolic acid liposomes (F-PEG-L-UA) on human epidermoid carcinoma xenografts in nude mice was also studied. RESULTS: Compared with free ursolic acid liposome, UA liposome was slowly removed from blood circulation and the concentration of F-PEG-L-UA in liver, kidney and tumor tissue is significantly higher than other groups. The growth speed of tumor in the group of F-PEG-L-UA was significantly slowed down compared with other groups. The tumor volume in F-PEG-L-UA group was about 50% reduction compared with PBS-treated mice (P<0.05). CONCLUSION: A novel targeted ursolic acid compound is synthesized as the folate receptor targeting functional material. It has obvious inhibitory effect on human epidermoid carcinoma xenografts and it might be an effective antitumor drug delivery system.