Peptide-drug conjugates (PDCs): a novel trend of research and development on targeted therapy, hype or hope?

Peptide-drug conjugates (PDCs) are the next generation of targeted therapeutics drug after antibody-drug conjugates (ADCs), with the core benefits of enhanced cellular permeability and improved drug selectivity. Two drugs are now approved for market by US Food and Drug Administration (FDA), and in the last two years, the pharmaceutical companies have been developing PDCs as targeted therapeutic candidates for cancer, coronavirus disease 2019 (COVID-19), metabolic diseases, and so on. The therapeutic benefits of PDCs are significant, but poor stability, low bioactivity, long research and development time, and slow clinical development process as therapeutic agents of PDC, how can we design PDCs more effectively and what is the future direction of PDCs? This review summarises the components and functions of PDCs for therapeutic, from drug target screening and PDC design improvement strategies to clinical applications to improve the permeability, targeting, and stability of the various components of PDCs. This holds great promise for the future of PDCs, such as bicyclic peptide‒toxin coupling or supramolecular nanostructures for peptide-conjugated drugs. The mode of drug delivery is determined according to the PDC design and current clinical trials are summarised. The way is shown for future PDC development.

Correlation and Clinical Significance of Ezrin and β-catenin Protein Expression in Sporadic Breast Cancer / 中国医科大学学报

Objective To explore the clinical significance of Ezrin and β?catenin in breast cancer. Methods Immunohistochemical staining method was adopted to detect Ezrin and β?catenin protein expression level in 145 cases of breast cancer tissues,and their correlation with clinical data and prognosis of breast cancer was analyzed. Results Ezrin was expressed in 70 cases(48.3%),β?catenin was expressed in 82 cases (56.6%),and there was significantly negative correlation(r=0.267,P=0.001). The higher histologic grade of breast cancer,the higher expres?sion level of Ezrin(P=0.007),and the lower expression level of β?catenin(P<0.001). Ezrin expression level was increased significantly(P=0.027),but β?catenin expression level was reduced significantly(P=0.011)in lymph node positive breast cancer tissue. Ezrin expression was sig?nificantly correlated with shorter overall survival(P=0.004)and disease free survival(P=0.017)of breast cancer patients,but β?catenin expres?sion was significantly correlated with longer overall survival(P<0.001)and disease free survival(P=0.001)of breast cancer patients. However , Ezrin and β?catenin were not the independent risk factors of breast cancer patients as determined by multivariate Cox regression. Conclusion Ez?rin was significantly negative correlated with β?catenin in breast cancer. They play a role in the progression and poor prognosis of breast cancer , which can be used as breast cancer treatment targets.

Protective Effect of ω-6 Soybean Oil Fat Emulsion on Folium Sennae-induced Diarrhea in Mice / 中国医科大学学报

Objective To investigate the protective effect of ω?6 soybean oil fat emulsion on folium sennae?induced diarrhea in mice. Methods Thirty?six Kunming mice were randomly divided into three groups,including control,diarrhea,ω?6 soybean oil fat emulsion group(12 mice in each group). Besides the mice in control group,other mice were administrated folium sennae by gavage for 15 days to establish the diarrhea model. Then mice in ω?6 soybean oil fat emulsion group received ω?6 soybean oil fat emulsion by intravenously administration at a dose of 15 mL/kg daily since 6th day after intragastric administration of folium sennae for 10 days. Animals in control group and diarrhea group were intravenously adminis?tered with same volume of saline. The body weight ,general state and diarrhea index of the mice in each group were dynamically assessed. Ten days after intravenous injection,mice in every group were sacrificed and tissues were collected. Morphology of intestine mucosa was observed after HE staining. Albumin(ALB)level in plasma was evaluated by biochemical method. Proliferating cell nuclear antigen(PCNA)expression in intestine mucosa were assessed by immunohistochemical method. Results Compared with that in the diarrhea group,the general status,body weight and diarrhea index of mice in ω?6 soybean oil fat emulsion group were improved significantly. Ten days after intravenously administration ,pathological change in intestine mucosa of mice in ω?6 soybean oil fat emulsion group was improved significantly ,ALB level in plasma and PCNA expression in intestine mucosa were significantly increased(P<0.05)compared with that in diarrhea group. Conclusion ω?6 soybean oil fat emulsion has a significant protective effect on the diarrhea of mice induced by folium sennae ,which may be related to the up?regulated expression of PCNA by ω?6 soybean oil fat emulsion.

The study on the role of salinomycin in the proliferation and epithelial-mesenchymal transition of breast cancer MCF-7 mammosphere cells / 天津医药

Objective To investigate the effects of salinomycin on the cell proliferation and epithelial-mesenchymal transition (EMT) of MCF-7 mammosphere (MCF-7 MS). Methods Breast cancer MCF-7 cells were cultured in suspension in serum-free medium to obtain MCF-7 MS. The cell viability of MCF-7 MS cells treated with serial concentrations of 0, 10, 30, 100, 300, 1 000, 3 000 and 10 000 nmol/L of salinomycin for 24 hours were detected by CCK-8 assay. The half maximal inhibitory concentration (IC50) was calculated. Western blot analysis was performed to detect the expression levels of E-cadherin and Snail in MCF-7 MS cells treated with 30 nmol/L and 60 nmol/L salinomycin. The same capacity of DMSO was added to MCF-7 MS as control group. The xenograft tumors from MCF-7 MS transplant mice were divided into control group (the same capacity of normal saline) and salinomycin group (5 mg/kg salinomycin), then the expressions of E-cadherin and Snail were dectected by immunohistochemical staining. Results With the increased concentration of salinomycin, the cell survival rate of MCF-7 MS cells decreased (P<0.05). The IC50 after 24 h-treatment was 989 nmol/L. Both 30 and 60 nmol/L of salinomycin increased the expression of E-cadherin and decreased the expression of Snail compared with control group. In addition, 60 nmol/L treatment group showed more significant effect (P<0.05). In xenograft tumors from MCF-7 MS transplant mice, the expression of Snail decreased, and E-cadherin increased in salinomycin treatment group compared with control group (P<0.01). Conclusion Salinomycin can inhibit the cell proliferation and EMT in MCF-7 MS cells, which is a potential drug to target cancer stem cells.

Preventive Effect of ω-6 Soybean Oil Fatty Emulsion on Gastric Ulcer in Rats / 医药导报

Objective To study the preventive effect ofω-6 soybean oil fatty emulsion on gastric ulcer caused by acetic acid in rat model, and investigate its mechanisms. Methods Thirty healthy rats were randomly and equally assigned to the following 3 groups:sham operation,gastric ulcer,andω-6 Soybean oil fatty emulsion group.The model was induced by acetic acid. Five days after the model was established successfully,rats in ω-6 soybean oil group received the treatment by tail intravenous injection with the dose of 10 mL.kg-1 .d-1 ,the sham operation group and gastric ulcer group were given the same dose of 0.9%sodium chloride solution.The rats were sacrificed at 10th day after the treatment.The pathological changes of rat gastric ulcer tissue were observed by HE staining, and the concentration of gastric acid was detected by acid-base neutralization method,as well as the activity of pepsin was detected by colorimetry.Serum NO concentration was detected with nitrate reductive enzymatic method, and the expression of EGFR in gastric mucosal was detected with immunohistochemical method. Results Gastric ulcer area inω-6 soybean oil fatty emulsion group (5.67±2.32 mm2) was significantly lower than that in gastric ulcer group(8.68±1.98 mm2). The concentration of gastric acid (1.70±0.53 mmol.L-1), activity of pepsin(23.12±6.97 U) and NO level (64.62±13.86μmol.L-1 ) inω-6 soybean oil fatty emulsion group were much lower than those in the model control group.While the expression of EGFR in gastric ulcer tissue was increased after treatment withω-6 soybean oil fatty emulsion. Conclusion ω-6 soybean oil fatty emulsion exerts significant promotion effect on the healing of gastric ulcer,and its mechanism might be related to inhibiting the level of gastric acid, pepsin and NO, while improving the protective effect of EGFR on gastric mucosa.

Clinical Significance of Ezrin Associated Subcellular Localization of E-cadherin Expression in Lymph Nodes Positive Breast Cancer / 中国医科大学学报

Objective To investigate the relationship between Ezrin expression and subcellular localization of E?cadherin(E?cad),and explore the clinical significance of this relationship to pathological features such as lymph nodes metastasis in breast cancer. Methods Ninety four cases of breast cancer tissue samples with lymph node metastasis were collected. The expression of Ezrin and E?cad was detected by immunohistochemi?cal method. Results The positive rates of and E?cad and Ezrin were respectively 45.7%and 58.5%in 94 nodes positive breast cancer,containing membranal expression of E?cad(E?cadm)in 20 cases and cytoplasmic expression of E?cad(E?cadc)in 23 cases;the frequency of E?cadc positive staining was significantly higher in Ezrin(+)tissues than that in Ezrin(-)tissues(P=0.025);E?cad expression level was significantly lower in TNMⅡ?Ⅲstage cases(P=0.001),and Ezrin expression(P=0.036)and E?cadc(P=0.013)was significantly increased in bigger cases;com?pared with E?cad(+),Ezrin(-),E?cadm tissues,the number of lymph node metastasis in E?cad(-)(P=0.011),Ezrin(+)(P=0.002),E?cadc (P=0.020)tissues were increased significantly;in the order of E?cad(+)/Ezrin(-),E?cad(-)/Ezrin(-),E?cad(+)/Ezrin(+),and E?cad(-)/Ezrin(+),the number of lymph node metastasis was increased significantly(P<0.001);similarly,in the order of E?cadm/Ezrin(-),E?cadc/Ezrin(-),E?cadm/Ezrin(+),and E?cadc/Ezrin(+),the number of lymph node metastasis was increased significantly(P=0.007). Conclusion Ezrin may regulate the subcellular localization of E?cad in metastatic breast cancer ,which may affect the course of breast cancer and promote the metastasis of lymph nodes.

The correlation of miR-100 expression with lymph node metastasis and FZD-8 protein expression in patients with breast cancer / 天津医药

Objective To evaluate the expression and relationship of miR-100 and FZD-8, one of the major compo?nents of Wnt signaling pathway, and the correlation of their expressions with lymph node metastasis in patients with breast cancer. Methods The expression of miR-100 was determined in 50 samples of human breast cancer tissues and adjacent normal tissues by in situ hybridization. The correlation of miR-100 expression with lymph node metastasis was analyzed by Mann-Whitney U test. The expression of FZD-8 was measured in 50 samples of human breast cancer tissues and adjacent normal tissues by immunohistochemistry. The correlation of the miR-100 expression with the protein expression of FZD-8 was evaluated by Pearson rank analysis. Results The expression of miR-100 was significantly lower in human breast can?cer tissues than that in adjacent normal breast tissues [2.00 (1.00, 3.00) vs. 6.00 (3.50, 8.00)]. The miR-100 expression was lower in patients with lymph node metastasis than that in patients without lymph node metastasis [1.50 (1.00, 2.75) vs. 3.00 (2.00, 4.00)]. The expression of FZD-8 was significantly higher in human breast cancer tissues than that in adjacent normal breast tissues [8.00 (6.00, 9.00) vs. 6.00 (3.75, 9.00)]. The miR-100 expression was negatively correlated with the FZD-8 pro?tein expression in human breast cancer tissues (rs=-0.592, P<0.001). Conclusion The miR-100, as an anti-metastasis-miRNA, may involve in the metastasis of breast cancer, which may be related with the regulation of the expression of FZD-8.

The effects of tumor microenvironment on the development and progression of breast cancer / 天津医药

Tumor microenvironment (TME) plays a key role in the development and progression of tumors, such as pro?moting local drug resistance, immune escape, and distal metastasis. According to the TME of different individuals, accurate evaluation and selection of clinical medication can effectively control the malignant transformation of carcinoma in situ and metastatic cancer. At present, the main method to treat cancer is chemotherapy, TME can regulate the reaction of the tumor cells to the standard chemotherapy and target drug therapy, so the combination of the targeted TME therapy and chemothera?py will achieve better clinical efficacy. In this review, we summarized the mechanisms of TME in breast cancer, including ex?tracellular matrix, carcinoma-associated fibroblasts, carcinoma-associated macrophages, regulatory T cells and bone marrow mesenchymal stem cells, which providing a theoretical basis for the development of TME targeted therapy.

Memantine improves cognitive deficits by activiating NGF/TrkA signaling in APP/PS1 transgenic mice / 中国药理学通报

Aims To study the role of NGF/Trk A sig-naling pathway in Memantine ( MEM) improving APP/PS1 transgenic mice cognitive deficits and to explore its possible mechanisms. Methods Cognitive perform-ance was assessed by Morris water maze( MWM) , pas-sive avoidance test( PAT) and locomotivity test. Aβ1-42 protein levels were determined by immunohistochemis-try. The activities of AChE and ChAT were also exam-ined by ELISA and colorimetry. Western blot was used to detect the expression levels of NGF and its receptor TrkA and the downstream ERK pathway. Results MEM treatment significantly ameliorated the cognitive deficits, dramatically reduced the Aβ1-42 overexpres-sion. MEM increased the activity of choline acetyl-transferase( ChAT) , while decreased that of acetylcho-line esterase( AChE) . Moreover, MEM activiated NGF signaling by increasing the phosphorylation of TrkA fol-lowing the increased phosphorylation of c-Raf, ERK1/2 and downstream effector CREB after MEM treatment. Conclusion MEM treatment may activate the NGF/TrkA signaling in APP/PS1 mice to reduce amyloidosis and cognitive deficits.

Research progress of vaccine therapy in non-small cell lung cancer / 中国肿瘤临床

Immunotherapy, particularly lung cancer vaccine therapy, has advantages of less side effects and low costs over classi-cal therapies of lung cancer, such as surgery, radiotherapy, and chemotherapy, as well as the relatively new molecular targeting therapy. PhaseⅢclinical trial for many kinds of non-small cell lung cancer (NSCLC) vaccines is ongoing based on deeper understanding of im-mune system and the expression of tumor antigens. This review summarizes the development of NSCLC vaccines.

Protective Effect of Omega-3 Fish Oil Fat Emulsion on Cyclophosphamide-induced Gastric Mucosal Injury in Mice / 中国医科大学学报

Objective to investigate the protective effect of omega-3 fish oil fat emulsion on cyclophosphamide-induced gastric mucosal injury in mice. Methods Forty-five kunming mice were randomly divided into three groups as control,model,and omega-3 fish oil fat emulsion group(with 15 mice in each group). Mice of the two experiment groups were administrated with cyclophosphamide i.p. for 2 days to establish the damage model. then mice in omega-3 fish oil fat emulsion group received omega-3 fish oil fat emulsion at a dose of 15 mL/kg daily for 14 days. Meanwhile,the ani-mals in control group and model group were intravenously administered with the same volume of saline. the weight and food intake of the mice in each group were assessed daily. Five mice in each group were respectively sacrificed at day 1,day 7,day 14 after intravenous injection. Morphology of gastric mucosa was observed by HE staining and the activities of SOD and MAO in gastric mucosa were measured respectively by xanthine oxida-tion and ultraviolet spectrophotometry methods. Results Compared with the model group,the general status,nutritional status and the injury in stomach mucosa in omega-3 fish oil fat emulsion group were significantly improved. After 14 day′s treatment,the activities of SOD and MAO in gas-tric mucosa of mice in omega-3 fish oil fat emulsion group were significantly increased(P < 0.05)compared with model group. Conclusion omega-3 fish oil fat emulsion has a significant protective effect on the cyclophosphamide induced injury in gastric mucosa of mice,which may be related to the upregulation of MAO and SOD.

Role of hypoxia-induced factors in cancer development mediated by cancer stem cells / 天津医药

Hypoxia and hypoxia-induced factors (HIFs) are main regulators for tumor stem cells, metastasis-initiating cells and their differentiated progenies to adapt to the environment which lacks oxygen and nutrient in the process of cancer development. HIFs are up-regulated in many tumors, including leukemia, glioblastoma, melanoma, prostate cancer, breast cancer and pancreatic cancer, in where they are especially highly expressed in hypoxic regions. HIFs activation can induce expression of numerous stem cell related genes and multidrug resistance genes, which may play important roles in tumour and stem cell-mediated self-renewing, energy metabolism alternation, invasion, metastasis, angiogenesis and treatment resis?tance of neoplastic cells. Consequently, it will provide new clues for cancer therapy after investigating the role of HIFs in tar?geted regulation and metabolic pathway modulation in various stem cell-mediated tumor cells.

The association of DNMT3a, DNMT3b expression with the state of promoter methylation of ERαgene and ERαexpression in sporadic breast cancer / 天津医药

Objective To investigate the correlationship between DNMT3a, DNMT3b protein expressions and the state of promoter methylation of ERα gene and ERα protein expression in the development of sporadic breast cancer. Methods A total of 180 patients with sporadic breast cancer and 30 patients with breast fibroadenoma were included in this study. The expressions of DNMT3a and DNMT3b protein were detected by immunohistochemical method. The state of promoter methylation of ERα gene was detected by methylation specific PCR in 97 patients with sporadic breast cancer. Results There were no significant differences in positive expression rates of DNMT3a and DNMT3b protein between breast fibroadenoma and breast cancer. There were higher expression levels of DNMT3a and DNMT3b in breast cancer patient of Ⅲ～Ⅳstages than those of Ⅰ～Ⅱstages. The expression of DNMT3a was significantly higher in patients with lymph node metastasis than that of patients without lymph node metastasis (P＜0.05). Of 97 cases of breast cancer patients, ERα gene promoter methylation occurred in 39 cases (40.2%). The positive expression of DNMT3a protein was positively correlated with the ERα gene methylation (rS=0.250). The DNMT3a protein expression showed a significant influence to the overall survival (OS) in patients of breast cancer (P=0.035), no significant influence to the disease-free survival (DFS) (P=0.064). DNMT3b protein expression showed no significant influence to OS and DFS of patients with breast cancer (P=0.914 and 0.961). Conclusion The positive expressions of DNMT3a and DNMT3b are correlated with the invasion, metastasis and poor prognosis of sporadic breast cancer. DNMT3a was positively correlated with the state of ERα gene promoter methylation. The inhibition of DNMT3a and DNMT3b may have advantages in the prevention and treatment of sporadic breast cancer.

EGCG ameliorating learning and memory impairment in APP/PS1 mice by inhibiting p75 NTR pathway / 中国药理学通报

Aim To investigate whether EGCG treat-ment ameliorates cognitive deficits in APP/PS1 trans-genic mice and, whether it has the ameliorating effect of p75 NTR signaling to neuronal apoptosis in the hippo-campus of APP/PS1 mice. Methods Morris water maze test and locomotivity test were used to predict be-havioral changes; further TUNEL staining and Fluoro-Jade B staining were applied to confirm the neuronal apoptosis and neuronal degeneration;Western blot was employed to detect protein expression levels of p75 NTR signaling in the hippocampus of APP/PS1 mice. Re-sults EGCG treatment dramatically ameliorated the cognitive impairments, and inhibited the neuronal ap-optosis in the APP/PS1 mice. Moreover, EGCG treat-ment dramatically inhibited the p75 NTR signaling by de-creasing the p75ICD expression, JNK2 phosphorylation, and cleaved-caspase 3 expression. Conclusion EGCG treatment dramatically ameliorates the cognitive impairments, and inhibits the neuronal apoptosis by in-hibiting the p75NTR signaling.

Regulatory effect of miR-181 a on breast cancer resistance protein / 中国药理学通报

Aim ToinvestigatetheeffectsofmiRNA-181 a on breast cancer resistance protein ( BCRP ) . Methods Bioinformaticspredictedbindingsitesof BCRP mRNA-3ˊUTR region and miR-181 a;further lu-ciferase reporter gene analysis confirmed that miR-181 a could combine with BCRP mRNA-3ˊUTR; qRT-PCR and Western blot detected related mRNA and protein expressionlevels.Results Comparedwithnegative transfection group, after the miR-181a mimic and PGL3-BCRP 3ˊUTR were co-transfected, luciferase ac-tivity was significantly decreased ( P 0. 05 ); after transfecting miR-181 a inhibitor for 48h, compared to the negative group, the expression of miR-181 a in MCF-7 cells was reduced (P0.05).Conclusion miR-181acanregu-late BCRP expression by targeting the BCRP mRNA-3ˊUTR region.

Research advances in the miRNA regulation of autophagy / 中国肿瘤临床

MicroRNAs are endogenously expressed non-coding RNAs, which are composed of approximately 18 nucleotides to 25 nucleotides. Mature microRNAs regulate gene expression by base pairing with the 3'-untranslated region of target mRNAs. These mature microRNAs can degrade target mRNAs or inhibit translation. This process is a type of post-transcriptional regulation of gene ex-pression. Studies have shown that microRNAs are important in physiological and pathological processes, such as cell proliferation, cell differentiation, and cell death. This article provides an overview of the function of microRNAs in the regulation of macrophages.

Changes of pulmonary function after bone injury treated with polymethylme-thacrylic bone cement / 中国组织工程研究

10.3969/j.issn.2095-4344.2013.25.023

Silencing of Fanconi Anemia Complementation Group F Exhibits Potent Chemosensitization of Mitomycin C Activity in Breast Cancer Cells / 한국유방암학회지

PURPOSE: Fanconi anemia complementation group F (FANCF) is a key factor to maintaining the function of Fanconi anaemia/BRCA (FA/BRCA) pathway, a DNA-damage response pathway. However, the functional role of FANCF in breast cancer has not been elucidated. In the present study, we evaluated the chemosensitization effect of FANCF in breast cancer cells. METHODS: We performed specific knockdown of the endogenous FANCF in breast cancer cells by transfecting the cells with an FANCF short hairpin RNA (shRNA) vector. Cell viability was measured with a Cell Counting Kit-8, and DNA damage was assessed with the alkaline comet assay. The apoptosis, cell cycle, and drug accumulation were measured by flow cytometric analysis. Protein expression levels were determined by Western blot analysis, using specific antibodies. RESULTS: The analyses of two breast cancer cell lines (MCF-7 and MDA-MB-435S) demonstrated that the FANCF shRNA could effectively block the FA/BRCA pathway through the inhibition of Fanconi anemia complementation group D2 ubiquitination. Moreover, FANCF silencing potentiated the sensitivity of cells to mitomycin C (MMC), where combined FANCF shRNA/MMC treatment inhibited cell proliferation, induced S-phase arrest, apoptosis, and DNA fragmentation, and reduced the mitochondrial membrane potential, compared with MMC treatment alone. CONCLUSION: Taken together, this study demonstrates that the inhibition of FANCF by its shRNA leads to a synergistic enhancement of MMC cytotoxicity in breast cancer cells. These results suggest that the inhibition of the FA/BRCA pathway is a useful adjunct to cytotoxic chemotherapy for the treatment of breast cancer.

The Correlation between the Inhibiting Effects of Irinotecan on Colorectal Cancer Cell Proliferation and ATP -sensitive Potassium Channel / 中国医科大学学报

Objective To study the effects of Irinotecan (CPT-11) on human colorectal cancer HCT-116 and HT-29 cells and investigate the potential mechanisms.Methods The effect of Irinotecan on the proliferation of HCT-116 and HT-29 cells was determined by MTT assays.The invasive capacity was measured by transwell assays,and the apoptosis of the tumor cells was detected by flow cytometry after stained with Annexin-V and PI.The difference between the current of ATP-sensitive potassium ion of HCT-116 and HT-29 was examined by patch clamp.Results It was found that 1.0-64.0 μg/ml CPT-11 could inhibit the proliferation and the invasive capacity of HCT-116 and HT-29 cells at both dose-and time-dependent manner.The IC_(50) of HCT-116 and HT-29 were 39.3 and 19.5 μg/ml respectively.Cytometry showed that the apoptotic rates were increased from 14.8% and 9.3% to 36.9% and 27.9% after the treatment of 32.0 μg/ml and 16.0 μg/ ml CPT-11,which were close to their IC_(50).The proportion of G_0/G_1 and S of HCT-116 and HT-29 was enhanced from 27.4% and 17.4% to 95.9% and 98.2%.Transwell assay indicated that the invasiveness of HCT-116 and HT-29 was reduced by 40.8% and 47.5%.The patch clamp showed that CPT-11 reduced the I_(KATP) of cell membrane at a negative dose-dependent manner.Conclusion CPT-11 could have a significant impact on the proliferation,invasiveness,cell cycle,and the apoptosis of human colorectal cancer cell HCT-116 and HT-29.HT-29 was more sensitive to CPT-11 than HCT-116.The inhibitory effect of CPT-11 on cell proliferation might be linked to its inhibition of ATPsensitive potassium channel.

The Effect of Docetaxel Combined with 4-AP on Human Breast Cancer MCF-7 Cells / 中国肿瘤临床

Objective: To study the effect of docetaxet (DOC) combined with 4-AP on human breast can-cer MCF-7 cells and to explore whether 4-AP could strengthen the effect of docetaxel. Methods: MTT assays were performed to investigate the effect of docetaxel, 4-AP and the combination of them on the proliferation of MCF-7 cells. Flow cytometry was employed to detect cell cycles and cell apoptosis after the cells were stained by PI alone or by Annexin-V and PI. Results: Docetaxel could significantly inhibit the proliferation of MCF-7 cells in a dose- and time- dependent manner. 4-AP could inhibit the proliferation of MCF-7 cells and the inhibitory rates were 11.9%±1.7%, 42.1%±3.2%, and 44.2%±1.6% at 24h, 48h and 72h after adding 4-AP. Moreover 4-AP (5mmol/L) could strengthen the effect of docetaxel. 4-AP (25μmol/L) could increase the effect of Docetaxel. Docetaxel at 5μmol/L could significantly increase the percentage of cells at G_2/M (53.58%± 1.44% vs. 8.83%±0.44%, P<0.01) and decrease the percentage of cells at G_0/G_1 (11.48%±0.14% vs. 63.89%±0.98%, P<0.01), indicating that docetaxel blocked MCF-7 cells at G_2/M phase. 4-AP at 5mmol/L could in-crease the percentage of MCF-7 cells at G_0/G_1 and decrease the percentage of cells at G_2/M (0.42%±0.17% vs. 8.83%±0.44%, P<0.05). Docetaxel could significantly increase late apoptosis and death of MCF-7 cells af-ter treatment over 24h (from 6.97%±0.75% to 20.77%±0.75%, P<0.05). Docetaxel combined with 4-AP could increase early apoptosis rate from 4.60%±0.91% to 12.20%±0.82% (P<0.05) and could increase late apopto-sis rate and death rate from 4.60%±0.91% to 12.20%±0.82% (P<0.05). Conclusion: Both docetaxel and 4-AP can inhibit the proliferation of MCF-7 cells. Docetaxel can increase the percentage of cells at G_2/M phase and 4-AP can increase the percentage of cells at G_0/G_1 phase. 4-AP could strengthen the inhibitory effect of docetaxel on the proliferation of MCF-7 cells through inducing cell apoptosis.