Small molecule inhibitor targeting the Hsp70-Bim protein-protein interaction in estrogen receptor-positive breast cancer overcomes tamoxifen resistance.

INTRODUCTION: Estrogen receptor (ER) positive patients compromise about 70% of breast cancers. Tamoxifen, an antagonist of ERα66 (the classic ER), is the most effective and the standard first-line drug. However, its efficacy is limited by the development of acquired resistance. METHODS: A specific inhibitor of Hsp70-Bim protein-protein interaction (PPI), S1g-2, together with an inhibitor of Hsp70-Bag3 PPI, MKT-077 and an ATP-competitive inhibitor VER155008, were used as chemical tools. Cell viability assays, co-immunoprecipitation and gene knockdown were used to investigate the role of Hsp70 in tamoxifen resistance. A xenograft model was established in which tamoxifen-resistant breast cancer (MCF-7/TAM-R) cells maintained in the presence of 5 µM tamoxifen were subcutaneously inoculated. The anti-tumor efficiency of S1g-2 was measured after a daily injection of 0.8 mg/kg for 14 days. RESULTS: It was revealed that Hsp70-Bim PPI protects ERα-positive breast cancer from tamoxifen-induced apoptosis through binding and stabilizing ERα36, rather than ERα66, resulting in sustained EGFR mRNA and protein expression. Disruption of Hsp70-Bim PPI and downregulation of ERα36 expression in tumor samples are consistent with the in vitro functions of S1g-2, resulting in about a three-fold reduction in tumor volume. CONCLUSIONS: The in vivo activity and safety of S1g-2 illustrated that it is a potential strategy for Hsp70-Bim disruption to overcome tamoxifen-resistant ER-positive breast cancer.

Preparation and in vitro release kinetics of nitrendipine-loaded PLLA-PEG-PLLA microparticles by supercritical solution impregnation process.

In this work, drug-loaded polymer microparticles were prepared by a supercritical solution impregnation (SSI) process with nitrendipine as the model drug and PLLA-PEG-PLLA as the drug carrier. The morphology, size, distribution and functional groups of the drug-loaded microparticles were characterized by scanning electron microscopy (SEM), laser particle size analyzer and fourier transform infrared analysis (FTIR). The effects of pressure, temperature and cosolvent concentration on the drug loading and release property of the microparticles prepared with and without cosolvent were investigated. The in vitro drug release kinetics of drug-loaded microparticles was studied with five models. The results indicated that the morphology of the drug-loaded polymer microparticles was not influenced by the SSI process. And the addition of ethanol cosolvent could significantly improve the drug loading of the microparticles. The most satisfied drug loading and the release properties of the microparticles were achieved under 55 °C, 13 MPa and cosolvent ethanol concentration of 3%. The drug could be released for more than 140 h. The analysis of the drug release kinetics showed that the experimental data fitted with Ritger-Peppas model were optimal. According to the release exponent value, the in vitro release process of the nitrendipine-loaded microparticles was controlled by Fickian diffusion, which can provides a theoretical basis for drug release of this type of experiment.

Correlations of insulin-like growth factor I and insulin-like growth factor I receptor with the clinicopathological features and prognosis of patients with colon cancer.

OBJECTIVE: This study is designed to evaluate the correlations of insulin-like growth factor I (IGF-I) and insulin-like growth factor I receptor (IGF-IR) expressions with the clinicopathological features and prognosis of patients with colon cancer. METHODS: From January 2010 to January 2009, tissue samples were collected from 121 colon cancer patients, 147 with colon adenoma and 63 patients with chronic diarrhea. Real-time quantitative polymerase chain reaction was used to analyze the mRNA expressions of IGF-I and IGF-IR. Immunohistochemistry was utilized to detect the protein expressions of IGF-I and IGF-IR. RESULTS: The IGF-I and IGF-IR mRNA expressions in colon cancer tissues were higher than those in colon adenoma tissues and normal tissues. The positive protein expressions of IGF-I and IGF-IR in colon cancer tissues were also higher than those in colon adenoma tissues and normal tissues. The mRNA expressions of IGF-I and IGF-IR were associated with the degree of differentiation, tumor node metastasis stage and lymphatic metastasis of colon cancer. Tumor node metastasis stage, lymphatic metastasis, postoperative chemotherapy and IGF-IR protein expression were independent factors for the prognosis of colon cancer. CONCLUSIONS: This study has demonstrated that overexpression of IGF-I and IGF-IR contributes to the development and progression of colon cancer.

Pttg1 inhibits TGFß signaling in breast cancer cells to promote their growth.

Increased expression of Pituitary Tumor Transforming Gene 1 (Pttg1) has been shown in various tumor cells, including breast cancer (BC). However, the precise role of Pttg1 in the tumorigenesis is not clarified yet. Here, we examined BC from the patients and detected significant increases and correlation in Pttg1 and phosphorylated SMAD3 (pSMAD3), a key effector of activated transforming growth factor ß (TGFß) receptor signaling pathway. Pttg1 levels were then modulated by transgene or small hairpin RNA (shRNA) in a human BC cell line, BT474, respectively. We found that Pttg1 overexpression increased the proliferation of BC cells in vitro and in vivo, while Pttg1 inhibition decreased proliferation of BC cells in vitro and in vivo. Moreover, phosphorylation of SMAD3 by TGFß1 was significantly inhibited by Pttg1 overexpression, suggesting that Pttg1 may promote growth of BC cells by inhibiting pSMAD3-mediated cell-growth inhibition. Thus, Pttg1 appears to be a novel therapeutic target for controlling the tumorigenesis of BC.

Peanut agglutinin appearance in the blood circulation after peanut ingestion mimics the action of endogenous galectin-3 to promote metastasis by interaction with cancer-associated MUC1.

Peanut agglutinin (PNA), which accounts for ~0.15% of the weight of the common peanut, is a carbohydrate-binding protein that binds the oncofoetal Thomsen-Friedenreich (TF) disaccharide (galactoseß1,3N-acetylgalactosamineα-) that is overexpressed by ~90% of human cancers. Previous studies have shown that PNA is highly resistant to cooking and digestion and rapidly enters the human blood circulation after peanut ingestion. This study investigates the hypothesis that PNA appearance in the circulation after peanut ingestion may mimic the actions of endogenous TF-binding human galectin-3 in metastasis promotion. It shows that PNA at concentrations similar to those found in blood circulation after peanut ingestion increases cancer cell heterotypic adhesion to the blood vascular endothelium and enhances the formation of tumour cell homotypic aggregates, two important steps in the metastasis cascade, and enhances metastasis in a mouse metastasis model. These effects of PNA are shown to result from its interaction with the cancer-associated TF disaccharide on the transmembrane mucin protein MUC1, causing MUC1 cell surface polarization that reveals underlying cell surface adhesion molecules. Thus, PNA appearance in the blood circulation after peanut ingestion mimics the actions of endogenous galectin-3 and promotes cancer cell metastatic spread by interaction with cancer-associated TF/MUC1. As metastasis accounts for the majority of cancer-associated fatality, regular consumption of peanuts by cancer patients would therefore be expected to have an adverse effect on cancer survival.

Revealing the molecular mechanism of colorectal cancer by establishing LGALS3-related protein-protein interaction network and identifying signaling pathways.

LGALS3 plays a role in colorectal cancer, however, the detailed molecular mechanism remains to be determined, while signaling pathways provide valuable information for understanding the underlying mechanism of the cancer. The purpose of this study was to explore the roles of LGALS3 and signaling pathways in the pathogenesis of colorectal cancer. In this study, microarray data GSE8671 were downloaded from the Gene Expression Omnibus database and differentially expressed genes (DEGs) in colorectal cancer were identified by Significant Analysis of Microarray. Gene ontology (GO) analysis was performed on the top 500 upregulated and 500 downregulated genes using DAVID. The signaling pathways were predicted by the signaling pathway impact analysis (SPIA) with pGFdr<0.05 and transcription factors were identified by TFats. The LGALS3-related protein-protein interaction network (PPI) was established by STRING and Cytoscape. In total, 6,593 upregulated and 5,897 downregulated DEGs were identified and 41 downregulated genes, including CLND8 and CLND23 were enriched in cell adhesion. In addition, 21 pathways, such as the cell cycle, p53 signaling pathway and NF-κB signaling pathway, were selected. MYC and TCF7L2 were found to be activated while FOXO3 was suppressed in colorectal cancer. Eight downregulated and 10 upregulated genes were identified in the LGALS3 PPI network. Results of the present study shed new light on the molecular mechanism of colorectal cancer and these findings have the potential to be used in colorectal cancer treatment.

Effect of nonionic compound emulsifiers Tween80 and Span80 on the properties of microencapsulated phase change materials.

In this article, the nonionic compound emulsifiers Tween80 and Span80 were used to prepare microcapsules containing phase change materials (microPCMs) with melamine-formaldehyde (MF) shells by in situ polymerization method. The effects of compound emulsifiers Tween80 and Span80 on the structure, morphologies and properties of microPCMs containing paraffin were studied. SEM morphological investigation suggests that a complex of Tween80 and Span80 as emulsifiers are optimal for the fabrication of microPCMs in this study compared to Tween60 or OP-10. The diameter distributions of microPCMs synthesized with different amounts of compound emulsifiers are uniform, whereas compound emulsifiers' amount affect the mean diameter of microPCMs decreasing from 5.34 to 3.05 µm. These microPCMs with the core/shell weight ratio 3/1 have smoother surface and a higher core content of 68.7% than other core/shell ratio. Anti-osmosis measurements indicate that microPCMs have good compactness and stable performance compared to those synthesized by one type of emulsifier.

Prognostic value of circulating tumor cells in patients with pancreatic cancer: a meta-analysis.

Increasing scientific evidences suggest that circulating tumor cells (CTC) in peripheral blood may be a powerful predictor of survival in patients with pancreatic cancer. However, many existing studies have yielded inconclusive results. This meta-analysis aims to assess the prognostic value of CTC in patients with pancreatic cancer. An extensive literary search for relevant studies was conducted on PubMed, Embase, Web of Science, Cochrane Library, CISCOM, CINAHL, Google Scholar, CNKI, and CBM databases from their inception through July 1, 2013. The meta-analysis was then performed using the Stata 12.0 software. Crude hazard ratios (HRs) with 95% confidence intervals (CIs) were calculated under a fixed or random effect model. Nine cohort studies were included in this meta-analysis with a total of 623 pancreatic cancer patients. This number included 268 CTC-positive patients and 355 CTC-negative patients. Our meta-analysis revealed that patients in the CTC-positive group were significantly associated with poor progression-free survival (PFS) (HR = 1.89, 95% CI = 1.25-4.00, P < 0.001). Furthermore, pancreatic cancer patients in the CTC-positive group also showed worse overall survival (OS) than those in the CTC-negative group (HR = 1.23, 95% CI = 0.88-2.08, P < 0.001). Subgroup analysis by ethnicity indicated that CTC-positive patients had poor OS among both Asian and Caucasian populations (all P < 0.05). Further subgroup analyses by detection and treatment methods also suggested that CTC-positive patients showed worser OS than CTC-negative patients in the majority of subgroups (all P < 0.05). No publication bias was detected in this meta-analysis. In conclusion, our meta-analysis suggests that CTC-positive pancreatic cancer patients may have worser PFS and OS than CTC-negative patients. Detection of CTC in peripheral blood may be a promising biomarker for the detection and prognosis of pancreatic cancer.

Increased circulation of galectin-3 in cancer induces secretion of metastasis-promoting cytokines from blood vascular endothelium.

PURPOSE: Cytokines such as interleukin (IL)-6 and granulocyte colony-stimulating factor (G-CSF) are important metastasis promoters. This study has investigated the functional significance of the increased circulation of galectin-3, a common feature in patients with cancer and in particular those with metastasis, on cytokine secretion from the blood vascular endothelium in cancer. EXPERIMENTAL DESIGN: The effects of galectin-3 on secretion of cytokines from human microvascular lung endothelial cells were assessed in vitro by cytokine array and in vivo in mice. The consequences of galectin-3-induced cytokine secretion on endothelial cell behaviors were determined, and the relationship between the levels of circulating galectin-3 and cytokines in patients with colorectal cancer with and without metastasis was investigated. RESULTS: Galectin-3 at pathologic concentrations found in patients with cancer induces secretion of IL-6, G-CSF, sICAM-1, and granulocyte macrophage colony-stimulating factor from blood vascular endothelial cells in vitro and in mice. These cytokines autocrinely/paracrinely interact with the vascular endothelium to increase the expressions of endothelial cell surface adhesion molecules integrinα(v)ß(1), E-selectin, ICAM-1, and VCAM-1, resulting in increased cancer cell-endothelial adhesion and increased endothelial cell migration and tubule formation. In patients with metastatic colon cancer, higher serum galectin-3 levels correlated significantly with increased serum G-CSF, IL-6, and sICAM1 concentrations. CONCLUSION: The increased circulation of galectin-3 in patients with cancer induces secretion of several metastasis-promoting cytokines from the blood vascular endothelium that enhances endothelial cell activities in metastasis. Targeting the actions of circulating galectin-3 in patients with cancer therefore represents a promising therapeutic strategy to reduce metastasis and improve survival.

Serum galectin-2, -4, and -8 are greatly increased in colon and breast cancer patients and promote cancer cell adhesion to blood vascular endothelium.

PURPOSE: Adhesion of disseminating tumor cells to the blood vascular endothelium is a pivotal step in metastasis. Previous investigations have shown that galectin-3 concentrations are increased in the bloodstream of patients with cancer and that galectin-3 promotes adhesion of disseminating tumor cells to vascular endothelium in vitro and experimental metastasis in vivo. This study determined the levels of galectin-1, -2, -3, -4, -8, and -9 in the sera of healthy people and patients with colon and breast cancer and assessed the influence of these galectins on cancer-endothelium adhesion. EXPERIMENTAL DESIGN: Serum galectins and auto-anti-MUC1 antibodies were assessed using ELISA and mucin protein (MUC1) glycan microarrays, and cancer-endothelium adhesion was determined using monolayers of human microvascular lung endothelial cells. RESULTS: The levels of serum galectin-2, -3, -4, and -8 were significantly increased up to 31-fold in patients with cancer and, in particular, those with metastases. As previously shown for galectin-3, the presence of these galectins enhances cancer-endothelium adhesion by interaction with the Thomsen-Friedenreich (TF; Galß1,3GalNAcα-) disaccharide on cancer-associated MUC1. This causes MUC1 cell surface polarization, thus exposing underlying adhesion molecules that promote cancer-endothelium adhesion. Elevated circulating galectin-2 levels were associated with increased mortality in patients with colorectal cancer, but this association was suppressed when anti-MUC1 antibodies with specificity for the TF epitope of MUC1 were also present in the circulation. CONCLUSIONS: Increased circulation of several members of the galectin family is common in patients with cancer and these may, like circulating galectin-3, also be involved in metastasis promotion.

Interaction between circulating galectin-3 and cancer-associated MUC1 enhances tumour cell homotypic aggregation and prevents anoikis.

BACKGROUND: Formation of tumour cell aggregation/emboli prolongs the survival of circulating tumour cells in the circulation, enhances their physical trapping in the micro-vasculature and thus increases metastatic spread of the cancer cells to remote sites. RESULTS: It shows here that the presence of the galactoside-binding galectin-3, whose concentration is markedly increased in the blood circulation of cancer patients, increases cancer cell homotypic aggregation under anchorage-independent conditions by interaction with the oncofetal Thomsen-Friedenreich carbohydrate (Galbeta1,3GalNAcalpha-, TF) antigen on the cancer-associated transmembrane mucin protein MUC1. The galectin-3-MUC1 interaction induces MUC1 cell surface polarization and exposure of the cell surface adhesion molecules including E-cadherin. The enhanced cancer cell homotypic aggregation by galectin-MUC1 interaction increases the survival of the tumour cells under anchorage-independent conditions by allowing them to avoid initiation of anoikis (suspension-induced apoptosis). CONCLUSION: These results suggest that the interaction between free circulating galectin-3 and cancer-associated MUC1 promotes embolus formation and survival of disseminating tumour cells in the circulation. This provides new information into our understanding of the molecular mechanisms of cancer cell haematogenous dissemination and suggests that targeting the interaction of circulating galectin-3 with MUC1 in the circulation may represent an effective therapeutic approach for preventing metastasis.

Circulating galectin-3 promotes metastasis by modifying MUC1 localization on cancer cell surface.

Adhesion of circulating tumor cells to the blood vessel endothelium is a critical step in cancer metastasis. We show in this study that galectin-3, the concentration of which is greatly increased in the circulation of cancer patients, increases cancer cell adhesion to macrovascular and microvascular endothelial cells under static and flow conditions, increases transendothelial invasion, and decreases the latency of experimental metastasis in athymic mice. These effects of galectin-3 are shown to be a consequence of its interaction with cancer-associated MUC1, which breaks the "protective shield" of the cell-surface MUC1 by causing MUC1 polarization, leading to exposure of smaller cell-surface adhesion molecules/ligands including CD44 and ligand(s) for E-selectin. Thus, the interaction in the bloodstream of cancer patients between circulating galectin-3 and cancer cells expressing MUC1 bearing the galectin-3 ligand TF (Galbeta1,3GalNAc-) promotes metastasis. This provides insight into the molecular regulation of metastasis and has important implications for the development of novel therapeutic strategies for prevention of metastasis.

Galectin-3 interaction with Thomsen-Friedenreich disaccharide on cancer-associated MUC1 causes increased cancer cell endothelial adhesion.

Patients with metastatic cancer commonly have increased serum galectin-3 concentrations, but it is not known whether this has any functional implications for cancer progression. We report that MUC1, a large transmembrane mucin protein that is overexpressed and aberrantly glycosylated in epithelial cancer, is a natural ligand for galectin-3. Recombinant galectin-3 at concentrations (0.2-1.0 microg/ml) similar to those found in the sera of patients with metastatic cancer increased adhesion of MUC1-expressing human breast (ZR-75-1) and colon (HT29-5F7) cancer cells to human umbilical vein endothelial cells (HUVEC) by 111% (111 +/- 21%, mean +/- S.D.) and 93% (93 +/- 17%), respectively. Recombinant galectin-3 also increased adhesion to HUVEC of MUC1 transfected HCA1.7+ human breast epithelial cells that express MUC1 bearing the oncofetal Thomsen-Friedenreich antigen (Galbeta1,3 GalNAc-alpha (TF)) but did not affect adhesion of MUC1-negative HCA1.7-cells. MUC1-transfected, Ras-transformed, canine kidney epithelial-like (MDE9.2+) cells, bearing MUC1 that predominantly carries sialyl-TF, only demonstrated an adhesive response to galectin-3 after sialidase pretreatment. Furthermore, galectin-3-mediated adhesion of HCA1.7+ to HUVEC was reduced by O-glycanase pretreatment of the cells to remove TF. Recombinant galectin-3 caused focal disappearance of cell surface MUC1 in HCA1.7+ cells, suggesting clustering of MUC1. Co-incubation with antibodies against E-Selectin or CD44H, but not integrin-beta1, ICAM-1 or VCAM-1, largely abolished the epithelial cell adhesion to HUVEC induced by galectin-3. Thus, galectin-3, by interacting with cancer-associated MUC1 via TF, promotes cancer cell adhesion to endothelium by revealing epithelial adhesion molecules that are otherwise concealed by MUC1. This suggests a critical role for circulating galectin-3 in cancer metastasis and highlights the functional importance of altered cell surface glycosylation in cancer progression.

Antitumor effect of Gefitinib, an epidermal growth factor receptor tyrosine kinase inhibitor, combined with cytotoxic agent on murine hepatocellular carcinoma.

AIM: To investigate the inhibitory effect of gefitinib combined with cytotoxic agent cisplatin (CDDP) on hepatocellular carcinoma (HCC). METHODS: Female Kunming mice and H22 hepatocarcinoma cells were used. Gefitinib at daily dose of 100 mg/kg body weight (BW) or lecithin liquid was given by gastrogavage once a day for 5 or 10 successive days. CDDP or normal saline (NS) was administered intraperitoneally (i.p.) once a day for 5 successive days. Mice were randomly divided into control group (lecithin, or NS, i.p.), CDDP group (daily dose, 1.2 mg/kg BW; d1-5, or d6-10), Gefitinib (d1-5, or d6-10, or d1-10), and Gefitinib combined with CDDP groups. The inhibitory rate (IR) of tumor, net BW, spleen index (SI), thymus index (TI) and the amount of peripheral blood cells of mice were detected on the 12th experiment day. RESULTS: The growth of HCC in mice was inhibited by Gefitinib alone (IR: 41% in d1-10 group and 30% in d1-5 group, respectively) or CDDP alone (IR: 32-54% in d1-5 group or d6-10 group). The highest inhibitory effect (IR: 56%) on HCC growth was observed in Gefitinib (d1-10) combined with CDDP (d1-5) group. Higher inhibition was also observed in CDDP (d1-5) followed by Gefitinib (d6-10) group than that in Gefitinib (d1-5) followed by CDDP (d6-10) group (IR: 61% vs 36%, P < 0.01) in the independent study. Net BW, SI, TI and the amount of blood cells of mice in Gefitinib alone group were not significantly different from those in control groups. CONCLUSION: Gefitinib can significantly inhibit the growth of murine H22 hepatocellular carcinoma. If Gefitinib is used after CDDP treatment in animal experiments, the inhibitory effect could be enhanced.

[The effect of IRESSA on H22 mouse hepatocellular carcinoma].

OBJECTIVE: To investigate the effect of IRESSA (gefitinib, ZD1839) on H22 murine hepatocellular carcinoma. METHODS: Mice bearing H22 hepatocellular carcinoma were randomly divided into oral control group, Normal saline (NS) control group, cisplatin (CDDP) d1-5 group, CDDP d6-10 group, IRESSA group, IRESSA combined with CDDP early (IRESSA + CDDP d1-5) group, and IRESSA combined with CDDP lately (IRESSA + CDDP d6-10) group. IRESSA was given by daily gastrogavage for 10 days (day 1-day 10) at 100 mg/kg in body weight (BW). CDDP was given by daily intraperitoneal injection for 5 days (day 1-day 5, or day 6-day 10) at 1.2 mg/kg in BW. The growth inhibiting rate (IR) of tumor, change of BW, spleen index (SI), and amounts of blood leucocyte or hemoglobin were detected. RESULTS: IR of tumor in IRESSA group was not significantly difference with that in CDDP d1-5 group, CDDP d6-10 group, IRESSA + CDDP d1-5 group (P > 0.05). IR of tumor in IRESSA group, CDDP d1-5 group, CDDP d6-10 group, IRESSA and IRESSA + CDDP d1-5 group were 41%, 54%, 46%, and 56%, respectively. IR of tumor in IRESSA + CDDP d6-10 group (26%) was significantly lower than that in CDDP d6-10 group (P < 0.05) or in IRESSA + CDDP d1-5 group (P < 0.01). Compared with oral or NS control groups, SI and net BW in IRESSA group was not significantly difference (P > 0.05). SI and net BW in both IRESSA + CDDP d1-5 group and IRESSA + CDDP d6-10 group were lower markedly than those in IRESSA group (P < 0.01). CONCLUSION: Tumor growth of H22 bearing mice was markedly inhibited by IRESSA.

[Enhancement of antioxidant capability of cancer patients during chemotherapy by reduced glutathione].

BACKGROUND & OBJECTIVE: It is unknown how administration of reduced glutathione (GSH) affects chemotherapy of cancer patients. This study was designed to investigate the effect of GSH on lipid peroxidation, and activities of antioxidant enzyme among cancer patients with chemotherapy. METHODS: Sixty-two cancer patients with chemotherapy were enrolled randomly into AB or BA group in cross-over pattern. In AB group, combination of chemotherapy and GSH was administrated first, then following chemotherapy alone was given 21 or 28 days later. In group BA, chemotherapy alone was administrated first, then the combination therapy was given. Duration of chemotherapy was 2-5 days, 21-28 days for a cycle, depended on chemotherapy strategies. GSH was given as a 15 minute intravenous infusion at the dose of 1 500 mgx(m(2)xd)(-1) for 7 days from day 1. Serum samples were collected from the patients on the day just before the chemotherapy, the 7(th) day, and the 21(st) (if 21 days per cycle of the chemotherapy) or 28(th) day of treatment. Concentration of malondialdehyde (MDA), activity of glutathione peroxidase (GSH-Px), and total superoxide dismutase (T-SOD) of serum samples were analyzed biochemically. RESULTS: (1)Administration of chemotherapy significantly increased serum MDA level on the 7(th) day compared with that before chemotherapy (mean+/-SD,6.12+/-1.94 micromol/L versus 4.63+/-1.87 micromol/L,P< 0.01). The increased serum MDA level was restored partially (5.05+/-2.07)micromol/L on the 21(th) or 28(th) day, but still higher than that before chemotherapy (P< 0.05). (2)Serum activity of T-SOD and GSH-Px decreased on the 7(th) day (P< 0.01) and restored partially on the 21(th) or 28th day, but still lower than that before chemotherapy (T-SOD, P< 0.05;GSH-Px,P< 0.01).(3)Co-treatment of GSH prevents lipid peroxidation and depletion of antioxidant enzymes by chemotherapy partially but significantly (P< 0.01). (4)Similar results were obtained in both AB group and BA group. CONCLUSION: Chemotherapy depletes antioxidant capability of cancer patients and co- treatment of GSH might prevent such depletion.