Nrf2 participates in mechanisms for reducing the toxicity and enhancing the antitumour effect of Radix Tripterygium wilfordii to S180-bearing mice by herbal-processing technology.

Context: Radix Tripterygium wilfordii Hook. f. (Celastraceae) (LGT) has outstanding curative efficacy; however, side effects include high toxicity, particularly hepatotoxicity and nephrotoxicity. Objective: To investigate detoxification mechanisms of LGT through processing separately with each of these medicinal herbs including Flower Lonicera japonica Thunb. (Caprifoliaceae) (JYH), Radix Paeonia lactiflora Pall. (Ranunculaceae) (BS), Herba Lysimachia christinae Hance (Primulaceae) (JQC), Radix et Rhizoma Glycyrrhiza uralensis Fisch. (Fabaceae) (GC) and Seed Phaseolus radiatus L. (Fabaceae) (LD) in S180-bearing mice by involving nuclear factor (erythroid-derived 2)-like 2 (Nrf2). Materials and methods: LGT raw and processed products were orally administered at 60 mg/kg to KM male mice inoculated with S180 tumour cells for 14 consecutive days, and blood, tumour, liver and kidney were taken to observe the detoxifying effects and biological mechanisms. Results: Herbal-processing technology significantly weakened hepatotoxicity and nephrotoxicity evoked by LGT with ED50 of the converted triptolide in each processed-herb product for serum alanine transaminase, aspartate transaminase, creatinine and urea nitrogen of 9.3, 16.6, 2.5 and 4.2 µg/kg, for liver glutathione, glutathione S-transferase, catalase, tumour necrosis factor-α and interleukin-10 of 114.9, 67.8, 134.1, 7.7, 4171.6 µg/kg, and for kidney 21.9, 20.5, 145.0, 529.7, 19.4 µg/kg, respectively. Moreover, herbal-processing technology promoted the accumulation of Nrf2 into the nucleus, and upregulated mRNA expression of Nrf2 and heme oxygenase-1. Additionally, herbal-processing technology enhanced the tumour inhibition rate with ED50 12.2 µg/kg. Discussion and conclusions: Herbal-processing technology improves the safety and effectiveness of LGT in cancer treatment, and future research may be focused on the Nrf2-related molecules.

(-)-Epigallocatechin-3-gallate alleviates doxorubicin-induced cardiotoxicity in sarcoma 180 tumor-bearing mice.

AIMS: (-)-Epigallocatechin-3-gallate (EGCG), a major green tea polyphenol compound, plays an important role in the prevention of cardiovascular disease and cancer. The present study aimed to investigate the effects of EGCG on doxorubicin (DOX)-induced cardiotoxicity in Sarcoma 180 (S180) tumor-bearing mice. MAIN METHODS: S180 tumor-bearing mice were established by subcutaneous inoculation of S180 cells attached to the axillary region. The extent of myocardial injury was accessed by the amount of lactate dehydrogenase (LDH) released in serum. Heart tissue was morphologically studied with transmission electron microscopy. Apoptosis, reactive oxygen species (ROS) generation, mitochondrial membrane potential (ΔÑ°m) as well as calcium concentration were measured by flow cytometric analysis. Expression levels of manganese superoxide dismutase (MnSOD) were analyzed by Western blot. KEY FINDINGS: Results showed that the combination with EGCG and DOX significantly inhibited tumor growth and enhanced induction of apoptosis compared with DOX alone. Moreover, administration of EGCG could suppress DOX-induced cardiotoxicity as evidenced by alleviating LDH release and apoptosis in cardiomyocyte. EGCG-evoked cardioprotection was in association with the increase of ΔÑ°m and MnSOD expression. EGCG was also found to attenuate ROS generation and myocardial calcium overload in Sarcoma 180 tumor-bearing mice subjected to DOX. SIGNIFICANCE: EGCG alleviated DOX-induced cardiotoxicity possibly in part mediated by increasing of MnSOD and Ñ°m, reducing myocardial calcium overload and subsequently attenuating the apoptosis and LDH release. Our findings suggest that co-administration of EGCG and DOX have potential as a feasible strategy to mitigate cardiotoxicity of DOX without compromising its chemotherapeutic value.

A multi-functional nanoplatform for tumor synergistic phototherapy.

Phototherapy, which mainly includes photothermal treatment (PTT) and photodynamic treatment (PDT), is a photo-initiated, noninvasive and effective approach for cancer treatment. The high accumulation of photosensitizers (PSs) in a targeted tumor is still a major challenge for efficient light conversion, to generate reactive oxygen species (ROS) and local hyperthermia. In this study, a simple and efficient hyaluronic acid (HA)-modified nanoplatform (HA-TiO2@MWCNTs) with high tumor-targeting ability, excellent phototherapy efficiency, low light-associated side effects and good water solubility was developed. It could be an effective carrier to load hematoporphyrin monomethyl ether (HMME), owing to the tubular conjugate structure. Apart from this, the as-prepared TiO2@MWCNTs nanocomposites could also be used as PSs for tumor PTT and PDT. Those results in vitro and in vivo showed that the anti-tumor effect of this system-mediated PTT/PDT were significantly better than those of single treatment manner. In addition, this drug delivery system could realize high ratio of drug loading, sustained drug release, prolonged circulation in vivo and active targeted accumulation in tumor. These results suggest that HA-TiO2@MWCNTs/HMME has high potential for tumor synergistic phototherapy as a smart theranostic nanoplatform.

Design and Synthesis of Antitumor Heck-Coupled Sclareol Analogues: Modulation of BH3 Family Members by SS-12 in Autophagy and Apoptotic Cell Death.

Sclareol, a promising anticancer labdane diterpene, was isolated from Salvia sclarea. Keeping the basic stereochemistry-rich framework of the molecule intact, a method for the synthesis of novel sclareol analogues was designed using palladium(II)-catalyzed oxidative Heck coupling reaction in order to study their structure-activity relationship. Both sclareol and its derivatives showed an interesting cytotoxicity profile, with 15-(4-fluorophenyl)sclareol (SS-12) as the most potent analogue, having IC50 = 0.082 µM against PC-3 cells. It was found that SS-12 commonly interacts with Bcl-2 and Beclin 1 BH3 domain proteins and enhances autophagic flux by modulating autophagy-related proteins. Moreover, inhibition of autophagy by autophagy inhibitors protected against SS-12-induced apoptosis. Finally, SS-12 effectively suppressed tumor growth in vivo in Ehrlich's ascitic and solid Sarcoma-180 mouse models.

Enhanced anticancer potential of encapsulated solid lipid nanoparticles of TPD: a novel triterpenediol from Boswellia serrata.

A pentacyclic triterpenediol (TPD) from Boswellia serrata has significant cytotoxic and apoptotic potential in a large number of human cancer cell lines. To enhance its anticancer potential, it was successfully formulated into solid lipid nanoparticles (SLNs) by the microemulsion method with 75% drug entrapment efficiency. SEM and TEM studies indicated that TPD-SLNs were regular, solid, and spherical particles in the range of 100-200 nm, and the system indicated that they were more or less stable upon storing up to six months. TPD loaded SLNs showed significantly higher cytotoxic/antitumor potential than the parent drug. TPD-SLNs have 40-60% higher cytotoxic and apoptotic potential than the parent drug in terms of IC(50), extent of apoptosis, DNA damage, and expression of pro-apoptotic proteins like TNF-R1, cytochrome-c, and PARP cleavage in HL-60 cells. Moreover, blank SLNs did not have any cytotoxic effect on the cancer as well as in normal mouse peritoneal macrophages. The in vivo antitumor potential of TPD-SLNs was significantly higher than that of TPD alone in Sarcoma-180 solid tumor bearing mice. Therefore, SLNs of TPD successfully increased the apoptotic and anticancer potential of TPD at comparable doses (both in vitro and in vivo). This work provides new insight into improvising the therapeutic efficacy of TPD by adopting novel delivery strategies such as solid lipid nanoparticles.

[Experimental study on inhibitory effect of GFW on transplantable tumor cell metastasis in S180 tumor-bearing mices].

OBJECTIVE: To detect the effect of GFW on tumor cell metastasis in S180 tumor-bearing mice. METHOD: S180 tumor-bearing mice model were replicated and divided randomly into 4 groups: the model group, the GFW group, the cyclophosphamide group and the combination administration group. VEGF in serum on each group was detected by ELISA, and the expression of metastasis suppressor gene nm23H1 and cell adhesion molecule CD44 in Sarcoma were detected by SABC immunohistochemical assay. RESULT: Compared with the model group, the GFW group showed a significant decrease in VEGF in serum (P < 0.01). From their statistically significant difference, GFW was proved to promote the expression of metastasis suppressor gene nm23H1 and inhibit the expression of cell adhesion molecule CD44 (P < 0.05). CONCLUSION: GFW has an effect on inhibiting tumor metastasis to some extent.

Extracts of Lycoris aurea induce apoptosis in murine sarcoma S180 cells.

Lycoris species have been known since long ago as a multi-utility ethnomedicinal herbal in China. It has been reported to exhibit a number of properties such as anticancer, neuroprotective, and antibacterial activities. In the present study, the anticancer efficacy of dichloromethane extracts of Lycoris aurea (DELA), was evaluated both in vivo and in vitro using murine sarcoma 180 cells. To evaluate the effects of DELA on apoptotic cell death, flow cytometry and Western blotting were performed. DELA demonstrated promising inhibition effects on sarcoma 180 cells in vitro and a 53.49% inhibitory rate on cancer cells in vivo. DELA treatment increased thymus indices and spleen indices in vivo, indicating that it reduced tumours, but did not damage the main immune organs. The DELA-evoked increase in apoptotic cell death was accompanied by occurrence of cleaved caspase-3 and decreases in the ratio of Bcl-2/Bax. Further purification and LCMS analysis showed DELA contained homolycorine, 2α-hydroxyoduline, oduline, hippeastrine, 2α-hydroxy-6-O- methyloduline, and 2α-methoxy-6-O-methyloduline. These results indicate that DELA exerted its anticancer effects, at least in part, by inducing cancer cell apoptosis and thus can be considered as a potential candidate agent for treatment of cancer.

[Anticancer activity of Crocodylus siamensis blood in vitro and in vivo].

OBJECTIVE: To study the anticancer effects of the blood of Crocodylus siamensis in vitro and in vivo. METHODS: The inhibitory effects of serum and plasma of Crocodylus siamensis on proliferation of HepG2, BGC823, HeLa and SKOV3 cell were measured by MTT assay. The mouse S180 tumor model was used to evaluate the anti-tumor effect in vivo. RESULTS: High dosage serum and plasma of Crocodylus siamensis could inhibit the proliferation of HepG2, BGC823, HeLa and SKOV3 cell. The tumor inhibitory rate of high dosage blood of Crocodylus siamensis on S180 tumor was up to 57.55%. CONCLUSION: The blood of breeding Crocodylus siamensis has anticancer activity.

[Polysaccharides from Scurrula parasitica L. inhibit sarcoma S180 growth in mice].

To study the anti-tumor activity of Scurrula parasitica polysaccharides (SP). Water extraction and ethanol precipitation were used to isolate SP from S. parasitica leaf. S180, K562 and HL-60 cell lines proliferation inhibition by SP were detected by MTT assay. The expressions of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP+ SP could not inhibit cancer cell proliferation. SP ip could inhibit the growth of sarcoma S180 in mice, 100 mg x kg(-1) x d(-1). SP ip was the optimal dose on inhibiting S180 growth, with the tumor inhibition rate of 54%. The expression of Ki-67, Cyclin D1, Bax and Bcl-2 protein in the sarcoma S180 tissues were detected by immunohistochemistry technique to approach the anti-tumor mechanism of SP. The result showed that SP could down-regulate the expression of Ki-67, CyclinD1 and Bcl-2 protein, and up-regulate the expression of Bax protein. It indicted that inhibiting cancer cell proliferation and promoting cancer cell apoptosis in vivo maybe one of the anti-cancer mechanisms of SP.

Cancer preventive effect of Kumaizasa bamboo leaf extracts administered prior to carcinogenesis or cancer inoculation.

BACKGROUND: Kumaizasa bamboo found in Hokkaido is used for traditional medicine in Japan. The cancer preventive effect of vigorous (multistep) hot water extract of Kumaizasa was examined in relation to immunological conditioning and free radical scavenging activity. MATERIALS AND METHODS: Cytokine induction in mice, free radical scavenging activity in vitro, and cancer preventive effect by oral administration of the vigorous extracts prior to tumor implantation or carcinogenesis by 7,12-dimethylbenz[a]anthracene (DMBA) were examined. RESULTS: In tumor inoculated mouse models (S-180 sarcoma, Meth-A fibrosarcoma, B16-F10 melanoma), the vigorous extracts from Kumaizasa bamboo leaves suppressed tumor growth and prolonged survival significantly. In the chemical carcinogenesis model suppression of cancer incidence on day 100, tumor size and survival time were significantly improved with the vigorous extract, at/or above 0.03% in the diet, when given two weeks prior to the administration of the carcinogen. CONCLUSION: The vigorous extracts of bamboo leaf show immunopotentiating and radical scavenging effects and administration prior to carcinogen exposure or tumor inoculation significantly suppresses tumor incidence and tumor growth and prolongs survival.

Antitumor effect and mechanism of Gecko on human esophageal carcinoma cell lines in vitro and xenografted sarcoma 180 in Kunming mice.

AIM: To investigate the anti-tumor effect of Chinese medicine Gecko on human esophageal carcinoma cell lines and xenografted sarcoma 180 in Kunming mice and its mechanism. METHODS: The serum pharmacological method was used in vitro. The growth rates of the human esophageal carcinoma cells (EC9706 or EC1) were measured by a modified 3-(4,5-Dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay. The transplanted tumor model of the mouse S180 sarcoma was established. Fifty mice were randomly divided into five groups (n=10). Three Gecko groups were treated respectively with oral administration of Gecko powder at a daily dose of 13.5 g/kg, 9 g/kg, and 4.5 g/kg. The negative group (NS group) was treated with oral administration of an equal volume of saline and the positive group (CTX group) was treated with 100 mg/kg Cytoxan by intraperitoneal injection at the first day. After 2 wk of treatment, the anti-tumor activity was evaluated by tumor tissue weighing. The impact on immune organ was detected based on the thymus index, spleen index, phagocytic rate and phagocytic index. The protein expression of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (bFGF) were detected by immunohistochemistry. The cell apoptotic rate was detected by terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick end labeling (TUNEL) assay. RESULTS: The OD value in each group treated with Gecko after 72 h was reduced significantly in EC9706 and in EC1. The tumor weight in each group of Gecko was decreased significantly (1.087+/-0.249 vs 2.167+/-0.592; 1.021+/-0.288 vs 2.167+/-0.592; 1.234+/-0.331 vs 2.167+/-0.592; P<0.01, respectively). However, the thymus index and Spleen index of mice in Gecko groups had no significant difference compared with the NS group. The immunoreactive score of VEGF and bFGF protein expression of each Gecko group by immunohistochemical staining were lowered significantly. The apoptosis index (AI) of each group was increased progressively with increase of dose of Gecko by TUNEL. CONCLUSION: Gecko has anti-tumor effects in vitro and in vivo; induction of tumor cell apoptosis and the down-regulation of protein expression of VEGF and bFGF may be contributed to anti-tumor effects of Gecko.

[Antitumor effect of polysaccharides from cactus pear fruit in S180-bearing mice].

BACKGROUND & OBJECTIVE: Polysaccharide components of some traditional Chinese medicine have certain antitumor effects and can promote immune responses. Extractions from cactus pear fruit can inhibit the proliferation of cervical cancer, ovary cancer and bladder cancer cells, and suppress the growth of ovarian cancer in mice. This study was to observe the antitumor effect of polysaccharides extracted from cactus pear fruit in S180-bearing mice. METHODS: S180-bearing mice were established and divided into five groups: normal saline (NS) group, cyclophosphamide (CTX) group, high, middle and low dose of polysaccharide groups. Tumor inhibition rates, values of thymus index, spleen index, superoxide dismutase (SOD), maleic dialdehyde (MDA) and nitrogen monoxidum (NO) were recorded. Changes in ultra-structures of tumor cells under transmission electron microscopy were observed. RESULTS: The tumor inhibition rates in CTX group, high, middle and low dose groups were 7.78%, 31.13%%, 49.70%, 61.07%, respectively. The thymus index was significantly higher in middle and high dose groups than in NS group [(2.61+/-0.43) mg x g(-1) and (2.65+/-0.73) mg x g(-1) vs. (2.22+/-0.24) mg x g(-1), P<0.05]. The spleen index of high dose group was higher than that of NS group [(6.45+/-0.97) mg x g(-1) vs. (5.42+/-1.13) mg x g(-1),P<0.05]. SOD of middle and high dose groups [(303.12+/-13.03) U/mL and (310.03+/-18.02) U/mL] were higher than that of NS group [(280.12+/-10.01) U/mL](P<0.05). MDA was lower in low, middle and high dose groups [(6.56+/-0.75) nmol/mL, (6.24+/-1.03) nmol/mL and (5.78+/-0.90) nmol/mL, respectively] than that in NS group [(7.39+/-0.51) nmol/mL] (P<0.05). NO was lower in low, middle and high dose groups [(56.12+/-8.60) micromol/L, (50.12+/-10.05) micromol/L, (48.06+/-8.45) micromol/L respectively] than in NS group [(64.14+/-1.25) micromol/L](P<0.05). Under electron microscopy, polysaccharide or CTX treated tumor cells showed typical morphology of early apoptosis with condensed chromatin at the margins of nuclei, disintegrated nucleolus and vacuoles in the cytoplasm. CONCLUSION: Polysaccharides extracted from cactus pear fruit possess certain antitumor effects, which can induce apoptosis, increase antioxidation and promote immune responses.

[Effect on mouse S180 MDR tumour cell expression correlated factorial matter by 70% ethanol with Huanglian Jiedu Tang].

OBJECTIVE: To observe the effect on P170, LRP, TOPO II of S180 tumour MDR mice for matter by 70% ethanol with Huanglian Jiedu Tang, and then discuss the molecular biology base for clinic. METHOD: 18-22 gramme mice were divided into four groups for normal S180 tumour cell group, matter by 70% ethanol with Huanglian Jiede Tang 100 mg x kg(-1) and 50 mg x kg(-1) in random. Each mouse was given S180 cell 0.2 mL by celiac, and after 24 hours give cisplatin for Injective 3 mg x kg(-1), ip, once a week. And give cyclophosphamide and 5-FU 3 mg x kg(-1), ig, once every day. After 15 days, collect lively mice ascites and give it for onefold normal mice. And then repeat before process. At the same time, every group was given corresponding medicine for 0.2 mL x 10 g(-1). The normal group and the model group were given the same cubage water, all together fore weeks. At last observd the P170, LRP, TOPO II by flow cytometry. RESULT: Matter by 70% ethanol with Huanglian Jiedu Tang could obviously reduce the express of P170 and LRP, and the activiation of TOPO II. CONCLUSION: Matter by 70% ethanol with Huanglian Jiedu Tang can intervene the ocurrence of the multi-drug resistance of tumour cells by regulating the biology gene.

[Effects of warming spleen and stomach for dispersing phlegm recipe on expression of interleukin-8 in S180 tumor tissue in mice].

OBJECTIVE: To observe the effects of warming spleen and stomach for dispersing phlegm recipe (Wenzhong Xiaotan Recipe, WZXTR), a compound traditional Chinese herbal medicine, on expression of interleukin-8 (IL-8) in S(180) tumor tissue in mice, and to explore the effectiveness and its mechanism. METHODS: Fifty mice were randomly divided into five groups: untreated group, cold water-treated group, cold water and WZXTR-treated group, cold water and dispersing phlegm and eliminating stagnation recipe (Xiaotan Sanjie Recipe, XTSJR, another compound traditional Chinese herbal medicine) treated group, cold water and tegafur-treated group. Mice in the latter 4 groups were fed 0-4 degrees centigrade cold distilled water 10 ml/(kg x d) one week before tumor inoculation for 3 weeks. Mice in the 5 groups were inoculated neoplastic cells which were diluted 2 x 10(7)/ml with normal saline in the right armpit at the second week. Forty-eight hours later, the mice were given drugs intragastrically (WZXTR, XTSJR and tegafur, respectively). The mice were continually intervened by cold water in the morning and given drugs in the afternoon. Mice in the cold water-treated group were given normal saline, and nothing was given in untreated group. Morphology appearance and changes of rectal temperature were observed, and the tumor weight and volume were measured and inhibitory rate was calculated 22 days after tumor inoculation. IL-8 was detected by avidin-biotin system-enzyme-labeled immunosorbent assay (ABC-ELISA) and real-time reverse polymerase chain reaction (real-time PCR). RESULTS: The content of IL-8 in tumor tissue of the untreated group was significantly higher than that of the other groups (P<0.01), and that of the cold water-treated group was higher than that of the cold water and WZXTR-treated group (P<0.01) and the cold water and XTSJR-treated group (P<0.05), respectively. The gray scale value of cDNA amplification strap was descent more evidently in both the cold water and WZXTR-treated group and the cold water and XTSJR-treated group as compared with that of the cold water-treated group and the untreated group (P<0.05). CONCLUSION: WZXTR can restrain tumor growth, and the mechanism may be that it can degrade the expression of IL-8 in S180 tumor.

[Study on depressant effects of THPS on S180 tumor-bearing-mice and its mechanisms].

OBJECTIVE: to study depressant effect of total hedysarum polybotys saccharids (THPS) on S180 tumor-bearing-mice and its mechanisms. METHODS: THPS was extracted from Radix Xedysari with water and precipitated with ethanol, determining its molecular weight, purity, saccharide and aldonic acid content. 90 Kunming mice were divided into 9 groups randomly. One group was the normal group, the others were divided into 8 groups randomly after inculating S180 tumors and were treated with THPS and THPS combination cyclophosphamide (CY) in low, moderate and high dose, to put them to death after 14 days. To determine every tumor weight, the rate of depressant tumor, the contents of IL-2 and TNF-alpha with ELISA, and NF-kappaB with immunochemistry. RESULTS: The moderate dose THPS conspicuously possessed a depressant effect on S180 tumor and joint action with combination CY and increased the contents of IL-2, TNF-alpha and NF-kappaB of mice. CONCLUSION: THPS of moderate dose possesses a depressant effect on S180 tumor through increasing the contents of IL-2, TNF-alpha and NF-kappaB of mice.

[The effect of tetrandrine on the expression of the P170, LRP and TOPO II in S180's tumor cell induced by chemotherapy in the mice with acquired multi-drug resistance].

OBJECTIVE: To observe the effect of tetrandrine on the P170 production expressed by multi-drug resistance gene, lung resistant protein (LRP), and topoisomeras II and elucidate the underlying molecular mechanism. METHOD: Cellular model of multi-drug resistance was established in S180 tumor cell by means of the scheme of PFC chemotherapy at the dosage lower than that with curative effect. P170, LRP and TOPO II were measured by flow cytometry after the mouse model was treated with tetrandrine for 4 weeks. RESULT: tetrandrine obviously reduced the enhancement of express of P170, LRP and the activity of TOPO II in the tumor cells with multi-drug resistance induced by chemotherapy. CONCLUSION: Tetrandrine significantly inhibits the multi-drug resistance of tumor cells induced by chemotherapy via diminishing both the expression of multi-drug resistance gene and the activity of topoisomeras II.

[Study on the effects of two kinds of cactus polysaccharide on erythrocyte immune function of S180 mice].

OBJECTIVE: To study the effects of two kinds of cactus polysaccharide on erythrocyte immune function in S180 mice. METHOD: Classical pharmaceutical method and test kit. RESULT: The cactus polysaccharide increased the content of RBC-CaR, RFER, decreased the content of RFIR, raised the content of sialic acid. And the effect of median dose group of medical cactus polysaccharide and high dose group of edible cactus polysaccharide is very remarkable (P < 0.01) compared with model group. CONCLUSION: The cactus polysaccharide improved the erythrocyte function of tumor-mice, which may be one of anti-tumor mechanisms.

[The study of tetrandrine on reversion of P170 and apoptosis of obtained multi-drug resistance of mice S180's tumour cell].

OBJECTIVE: To observe the effect of tetrandrine on reversion of mice S180's obtained multi-drug resistance tumor cell induced by chemotherapy by PFC. And then discuss the molecular mechanism of it for the use of TCM in clinic to restrain the drug-resistant of chemotherapy, thereby improve the curative effect. METHOD: By the methods of less dosage of chemotherapy PFC, give the mouse cisplatin 3 mg x kg(-1) i.p., once a week; CTX and 5-FU 3 mg x kg(-1) i.g. four weeks, set up the mice models of multi-drug resistance of S180 tumor cell, and then observe the P170, Fas, CD54 and apoposis by flow cytometry. RESULT: Tetrandrine can obviously lower the express of P170 increase the express of Fas and the apoposis of drug resistant tumor cell. And at the same time it can obviously reduce the express of intercellular adhesion molecule (CD54). CONCLUSION: Terandrine, with its adjustment of correlated biotic active matter, can intervene the occurrence of the multi-drug resistance of tumor cells induced by chemotherapy.

[The interference in correlated molecular mechanism obtained multi-drug resistance of mouse S180's tumour cell for different alkaloid].

OBJECTIVE: To observe the base of the interference in correlated biotic active matter obtained multi-drug resistance induced by chemotherapy for different alkaloid, and to supervise the use in clinic to restrain the multi-drug resistant of chemotherapy, and thereby to improve the curative effect. METHOD: After bestowing subter-dosage unite chemotherapeutant to ascites S180 mouse to set up the mouse models of multi-drug resistance of S180 tumour cell, and giving the mouse matrine, terandrine, oxymatrine and berberine hydrooh loride for 4 weeks, the P170, LRP, TOPOII, Fas and apoposis were determined by flow cytometry. RESULT: Matrine and terandrine could obviously reduce the express of P170, LRP and the activation of TOPOII, and increase the ratio of the express of Fas and the apoposis of drug resistant tumour cell. And at the same time it could obviously reduce the express of intercellular adhesion molecule(CD54). CONCLUSION: Matrine and terandrine can interfere in MDR which results from chemotherapeutics by the adjustment of correlated biotic active matter, besides, the different degree of alkaloid effect with different configuration.

[Salvianolic acid A inhibits nucleoside transport and potentiates the antitumor activity of chemotherapeutic drugs].

AIM: To investigate the inhibitory activity of salvianolic acid A (SAA) on nucleoside transport in cancer cells and its antitumor effect. METHODS: [3H] thymidine and [3H] uridine transport assays were used to determine the inhibitory activity on nucleoside transport in Ehrlich carcinoma cells. The cytotoxicity to cultured cancer cells was examined with clonogenic assay. The antitumor effect in vivo was evaluated with transplantable tumor model in mice. RESULTS: SAA was shown to inhibit thymidine and uridine transport in Ehrlich carcinoma cells with IC50 values of 18.1 and 17.1 micromol x L(-1), respectively. By clonogenic assay, the IC50 of SAA for KB cells was 44.7 micromol x L(-1). SAA markedly potentiated the cytotoxicity of 5-FU and mitomycin C in KB cells as well as the cytotoxicity of MTX in human hepatoma BEL-7402 cells. For in vivo experiment, sarcoma 180 cells were transplanted sc in mice and tested drugs were administered ip. When administered separately, SAA at 200 mg x kg(-1) and 5-FU at 10 mg x kg(-1) inhibited tumor growth by 41% and 27%, respectively. Combination of the two drugs inhibited tumor growth by 63% (CDI = 0.86). CONCLUSION: SAA is active in blocking nucleoside transport in cancer cells and potentiates the cytotoxicity of chemotherapeutic drugs. As an agent showing moderate antitumor effect in vivo, SAA might be useful in combination cancer therapy.