Network pharmacology and phytochemical composition combined with validation in vivo and in vitro reveal the mechanism of platycodonis radix ameliorating PM2.5-induced acute lung injury.

ETHNOPHARMACOLOGICAL RELEVANCE: Platycodonis radix (PR), the root of Platycodon grandiflorus (Jacq.) A. DC., is a traditional Chinese medicine recognized for its dual role as both a medicinal and dietary substance, exhibiting significant anti-inflammatory properties. It is frequently utilized in the treatment of lung diseases. However, the molecular mechanisms by which PR exerts its effects in the treatment of acute lung injury (ALI) remain unclear. AIM OF THE STUDY: This study presents a novel strategy that integrates network pharmacology, molecular docking, untargeted metabolomics analysis and experimental validation to investigate the molecular mechanisms through which PR treats ALI. MATERIALS AND METHOD: Initially, the bioactive components of PR, along with its targets and pathways in the treatment of ALI, were identified using network pharmacology. Following this, preliminary validation was conducted through molecular docking. The active ingredients in the aqueous extract of PR were characterized using HPLC-MS. Finally, in vivo and in vitro experiments were performed to further validate the findings from the network pharmacology. RESULTS: A total of 14 bioactive components and 156 effective targets were identified using the TCMSP, DisGeNET, Genecard, OMIM databases and Venny 2.1.0. Protein-protein interaction (PPI) analysis revealed 22 core targets including TP53, AKT1, STAT3 and JUN. Gene Ontology (GO) and Kyoto Encyclopedia of Genes and Genomes (KEGG) enrichment analyses indicated that these targets primarily participate in the regulation of cellular apoptosis, lung cancer and inflammatory pathways. Molecular docking demonstrated that four bioactive components exhibited strong affinities with their respective docking targets. LC-MS analysis confirmed that the aqueous extract of PR contained 87 components, including two active ingredients identified through network pharmacology and molecular docking. Preliminary validation was conducted in mice with ALI induced by acute PM2.5 exposure, revealing that the aqueous extract of PR reduced inflammatory factor levels in bronchoalveolar lavage fluid, enhanced antioxidant capacity in lung tissue, and decreased lung cell apoptosis in PM2.5-exposed mice. Notably, PR alleviated PM2.5-induced ALI through the STAT3, JUN, and AKT1 signaling pathways. Similarly, the results of in vitro intervention experiments further confirmed that the aqueous extract of PR protected pulmonary epithelial cells against PM2.5 exposure through activating AKT1 sinalling pathway, and inhibiting STAT3 and JUN signalling pathways. CONCLUSION: This study identifies the active components of PR and elucidates the molecular mechanisms by which PR alleviates ALI, specifically by inhibiting the phosphorylation levels of STAT3 and c-JUN, or by activating the phosphorylation level of AKT1. These results provide a foundational basis for the application of PR in the treatment or prevention of lung injuries induced by particulate matter.

The association of physical activity and sedentary behavior with depression in US adults: NHANES 2007-2018.

Objectives: Depression is largely preventable, and strategies that can effectively suppress its development are imperative. We aimed to examine whether physical activity and sedentary behavior were associated with depression and explore the possible mediatory role of complete blood count in this association. Methods: In this cross-sectional study, data were integrated from the National Health and Nutrition Examination Study (2007-2018). Depression was defined using the Patient Health Questionnaire-9. The risk for depression, expressed as odds ratio (OR) and 95% confidence interval (CI), was quantified by survey-weighted logistic regression analyses. Results: A total of 31,204 respondents were analyzed. Significance was identified for all, except walking or bicycling per week, types of physical activity, and sedentary behavior. Per 1 standard deviation (SD) increment in metabolic equivalent of task (MET) of weekly vigorous recreational physical activity was associated with 31.3% decreased depression risk (adjusted OR: 0.687, 95% CI: 0.5663-0.840). Per 1 SD increment in sitting time can increase depression risk by 22.4% (adjusted OR: 1.224, 95% CI: 1.131-1.325). In subsidiary analyses, the association with depression was reinforced in respondents aged ≤65 years and those overweight or obese. Mediation analyses revealed significant effects for red blood cell (RBC) on total MET (19.4%) and moderate work-related physical activity (MWPA) (22.0%), and for red cell distribution wide (RCDW) on vigorous work-related physical activity (17.7%), moderate work-related physical activity (13.1%), total MET (11.2%), and sitting time (16.4%) (p < 0.01). Conclusion: Our findings indicate that more physical activity and less sitting time were associated with a lower likelihood of having depression among US adults, and this association was probably mediated by RBC and RCDW.

Pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives as RAF-MEK-ERK pathway signaling pathway blockers: Synthesis, cytotoxic activity, mechanistic investigation and structure-activity relationships.

The constitutive activation of ERK1/2 (RAF-MEK-ERK) signaling pathway has been widely observed in many types of tumors, and the blockade of ERK1/2 signaling pathway has been proved to reduce tumor growth. Therefore, ERK1/2 signaling pathway has become an interesting therapeutic target for cancer therapy. Despite the successful development of BRAF and MEK inhibitors in clinic treatment, resistance often appears to re-enhance ERK1/2 signaling. Here we report the design, synthesis, biological activity of a series of novel pyrido[2,3-d]pyrimidine-2,4(1H,3H)-dione derivatives based on compound 1. Among them, the target compound N-(3-chlorophenyl)-2-((1,3-dimethyl-7-(4-methylpiperazin-1-yl)-2,4-dioxo-1,2,3,4-tetrahydropyrido[2,3-d]pyrimidin-5-yl)amino)acetamide (14m) exhibited excellent antiproliferative activity towards MCF-7, A375, SK-MEL-2 and SK-HEP-1 cells, with low cytotoxicity in C28/I2 cells. Tumor spheroid assay demonstrated the superior potency of 14m in inhibiting the growth of SK-HEP-1 spheroidal models. The mechanism of 14m to induce cancer cell death was shown to suppress cell migrations, induce cell apoptosis, decrease the levels of phosphorylated ERK and MEK in a dose-dependent manner and increase ROS production.

Effect of transjugular intrahepatic portosystemic shunt combined with 125I particle implantation on portal vein tumor thrombus in hepatocellular carcinoma.

OBJECTIVE: The efficacy of transjugular intrahepatic portosystemic shunt (TIPS) combined with 125I particle implantation in the treatment of portal vein tumor thrombus (PVTT) in hepatocellular carcinoma was discussed and analyzed in this study. METHODS: A total of 127 patients with primary hepatocellular carcinoma (PHC) complicated with PVTT admitted to our hospital from March 2017 to June 2018 were enrolled. The patients were classified into an observation group (n=69) and a control group (n=58) in the light of the different treatment methods. The control group patients were treated with TIPS alone, and the observation group patients received 125I particle implantation on the basis of TIPS in the control group. Subsequently, the clinical therapeutic efficacy, perioperative indicators, postoperative complications, quality of life and survival of patients before and after treatment were compared between the two groups. RESULTS: The remission rate in the observation group was remarkably higher than that of the control group (P<0.05), and the difference in the overall response rate (ORR) of the two groups of patients was not statistically significant (P>0.05). The AFP, PLT, WBC and the diameter of the main portal vein in the two groups dropped substantially compared to those before treatment (P<0.05), and the AFP and the diameter of the main portal vein in the observation group were notably lower than those in the control group (P<0.05). After treatment, the ALT, AST and TBiL of the two groups were remarkably higher than those before treatment (P<0.05), and these indicators in the observation group were apparently higher than those in the control group (P<0.05). There was no significant difference in the incidence of postoperative gastrointestinal bleeding, fever, granulocytopenia and abnormal hepatic dysfunction between the observation group and the control group (P>0.05). The functional assessment of cancer therapy-hepatobiliary (FACT-Hep) scores of the two groups 6 months after operation was substantially lower than pre-op scores (P<0.05), and the observation group had apparently lower postoperative scores than the control group (P<0.05). The progression-free survival (PFS) and overall survival (OS) in the observation group were critically superior to those in the control group (P<0.05). CONCLUSION: TIPS combined with 125I particle implantation in the treatment of PHC patients with PVTT can help improve patients' clinical treatment efficacy after surgery while prolonging their postoperative survival. The treatment is safe and worthy of clinical promotion.

The antifibrotic effect of pheretima protein is mediated by the TGF-ß1/Smad2/3 pathway and attenuates inflammation in bleomycin-induced idiopathic pulmonary fibrosis.

ETHNOPHARMACOLOGICAL RELEVANCE: Pheretima is a traditional Chinese medicine that could treat various lung diseases such as asthma, pneumonia, and lung cancer effectively; however, limited studies on the use of Pheretima protein in the treatment of lung diseases have been conducted to date. AIM OF THE STUDY: The aim of this study was to explain the antipulmonary fibrosis mechanism of the Pheretima protein and elucidate its possible cell signaling pathways. MATERIAL AND METHODS: Fresh pheretima was freeze-dried to obtain the Pheretima protein. Divide C57BL/6 mice into control and bleomycin (BLM)-induced models, pirfenidone, and Pheretima protein-treatment groups. Three weeks later, they were treated with H&E and Masson's trichrome staining to assess lung injury and fibrosis. Pulmonary fibrosis was assessed using immunohistochemistry (IHC), realtime-PCR (RT-PCR), and western blotting. Inflammation was assessed using the alveolar lavage fluid. RESULTS: Pheretima protein inhibited epithelial-mesenchymal transition (EMT) and extracellular matrix (ECM) deposition and reduced inflammation. It also reduced the levels of Smad2/3, pSmad2/3, and transforming growth factor-beta 1 (TGF-ß1). Thus, our results indicate that Pheretima protein can alleviate BLM-induced pulmonary fibrosis in a mouse model. CONCLUSION: Pheretima protein inhibits ECM, EMT, and antiinflammatory markers, which in turn ameliorates BLM-induced pulmonary fibrosis. Preliminary mechanistic studies indicated that Pheretima protein can exert its biological activity by downregulating the TGF-ß1/Smad2/3 pathway.

The Protective Activity of Penehyclidine Hydrochloride against Renal Ischemia/Reperfusion-Mediated NLRP3 Inflammasome Activation is Induced by SIRT1.

Background: The activation of alveolar macrophages (AMs) modulated via leucine-rich repeat (NLR) pyrin domain containing 3 (NLRP3) inflammasome activation is key to the progression of renal ischemia/reperfusion (rI/R)-mediated acute lung injury (ALI). Sirtuin-1 (SIRT1) can attenuate NLRP3 inflammasome activation during I/R stress and may be an important mechanism underlying ALI pathogenesis. Penehyclidine hydrochloride (PHC), an anticholinergic drug, exerts protective effects against rI/R-mediated ALI. This study aimed to decipher the effects of PHC on SIRT1 activation and the underlying mechanism of the protective activity of PHC against rI/R-mediated ALI.Materials and methods: We used an ALI rat model and the rat AMs cell line NR8383 to assess the degree of lung injury in vivo and in vitro.Results: The results show that PHC attenuates rI/R-mediated lung injury indices, myeloperoxidase, and apoptosis in vivo. It decreases the rI/R-mediated release of prostaglandin E2 and nitric oxide, mitochondrial reactive oxygen species production, and the activity of NADPH oxidase-4 in vitro. PHC ameliorates the rI/R-induced activation of the thioredoxin-interacting protein, caspase 1 (P10 unit), and NLRP3 inflammasome, along with reduced activation of interleukin-1ß and interleukin-18 in vitro. We show that PHC alleviates the rI/R-induced reduction of SIRT1 and the depletion of SIRT1 eliminates the ameliorating activity of PHC on the NLRP3 inflammasome activation in vitro. Conclusions: In summary, the findings suggest that PHC ameliorates the rI/R-mediated ALI through the SIRT1-mediated NLRP3 inflammasome activation.

Propofol ameliorates renal ischemia/reperfusion injury by enhancing macrophage M2 polarization through PPARγ/STAT3 signaling.

Propofol (Pro) confers protection against renal ischemia/reperfusion (rI/R) injury through incompletely characterized mechanisms. Since Pro has shown net anti-inflammatory properties as part of its beneficial effects, we examined the potential role of Pro in the modulation of macrophage polarization status during both rI/R injury in vivo and exposure of cultured peritoneal macrophages (PMs) to hypoxia/reoxygenation (H/R). Rats were subjected to 45-min r/IR surgery or a sham procedure and administered PBS (vehicle) or Pro during the ischemia stage. Pro administration attenuated rI/R-induced kidney damage and renal TNF-α, IL-6, and CXCL-10 expression. Enhanced macrophage M2 polarization, evidenced by reduced iNOS and increased Arg1 and Mrc1 mRNA levels, was further detected after Pro treatment both in the kidney, after rI/R in vivo, and in H/R-treated PMs. Pro administration also repressed phosphorylated signal transducer and activator of transcription 1 (p-STAT1) and increased p-STAT3, p-STAT6, and peroxisome proliferator-activated receptor-γ (PPARγ) mRNA levels in H/R-exposed PMs. Importantly, siRNA-mediated PPARγ silencing repressed Pro-mediated STAT3 activation in PMs and restored proinflammatory cytokine levels and prevented macrophage M2 marker expression in both rI/R-treated rats and cultured PMs. These findings suggest that Pro confers renoprotection against rI/R by stimulating PPARγ/STAT3-dependent macrophage conversion to the M2 phenotype.

MicroRNA-877 is downregulated in cervical cancer and directly targets MACC1 to inhibit cell proliferation and invasion.

Previously, a number of microRNAs (miRNAs) have been reported to be dysregulated in cervical cancer, and dysregulated miRNAs may play crucial roles in the development and progression of cervical cancer. Hence, investigating the detailed roles of miRNAs that are aberrantly expressed in cervical cancer and the underlying molecular mechanisms is essential for early diagnosis and effective therapeutic approaches. miRNA-877 (miR-877) was found to be downregulated in hepatocellular carcinoma and renal cell carcinoma, and function as a tumor-suppressive miRNA. However, how miR-877 exerts an effect in cervical cancer progression and its underlying molecular mechanisms remains to be elucidated. In the current study, reverse transcription-quantitative PCR was performed to determine miR-877 expression in cervical cancer tissues and cell lines. The effects of miR-877 overexpression on cervical cancer cell proliferation and invasion were evaluated using MTT and Transwell cell invasion assays. In the present study, miR-877 was significantly downregulated in cervical cancer tissues and cell lines, and the decreased expression levels of miR-877 were significantly associated with increased International Federation of Gynecology and Obstetric stage as well as increased lymph node metastasis in patients with cervical cancer. Upregulation of miR-877 using miR-877 mimics resulted in the decreased proliferation and invasion of cervical cancer cells. Metastasis-associated in colon cancer-1 (MACC1) was assessed using bioinformatics analyses to determine whether it could be a potential target gene of miR-877, and the results were confirmed using a luciferase reporter assay. Furthermore, MACC1 was markedly upregulated in cervical cancer tissues, and its level was negatively correlated with the miR-877 level. Overexpression of miR-877 resulted in decreased expression levels of MACC1 in cervical cancer cells at both the mRNA and protein levels. In addition, the functional effects of MACC1 knockdown were similar to those induced by upregulated miR-877 in cervical cancer cells. MACC1 restored miR-877 overexpression-mediated suppression of cervical cancer cell proliferation and invasion. In conclusion, miR-877 may play an antitumor role in cervical cancer by directly targeting MACC1, which suggests that this miRNA may be a promising therapeutic target for the treatment of patients with such an aggressive gynecological cancer.

Phenformin and metformin inhibit growth and migration of LN229 glioma cells in vitro and in vivo.

BACKGROUND: Malignant glioma is refractory to conventional treatment, highlighting a need to develop novel efficacious therapies. Biguanides, a class of oral antidiabetic drug, have been thought to inhibit proliferation and metastasis in a variety of cancers. PURPOSE: The objective of this study was to investigate the affections of biguanides, phenformin (Phen) and metformin (Met), on growth and migration of glioma cells LN229 in vitro and in vivo. METHODS: Glioma cells LN229 were treated with Phen or Met, then cell proliferation and death were evaluated by MTT assay and PI stain, and cell cycle were evaluated using flow cytometric analysis, meantime wound healing assay and transwell migration assay were performed to detect cell migration ability. In addition, LN229 were injected in thigh of nude mice, and the mice were treated with Phen or Met to detect the effect of Phen and Met in vivo. RESULTS: Phen and Met could significantly inhibit cell growth through inhibiting cell proliferation, promoting cell death and disturbing cell cycle, and these drugs also could inhibit cell colony formation in glioma cells LN229 in vitro. Meanwhile, both Phen and Met could significantly inhibit cell migration of LN229 in vitro, through effecting the expression of E-cadherin and Vimentin. In addition, both Phen and Met inhibited the growth and migration of LN229 in a tumor xenograft model. Furthermore, Phen and Met were associated with the increased level of ROS of cell mitochondrial, and ROS inhibitor NAC could significantly rescue the cell death induced by Phen and Met. CONCLUSION: Phen and Met displayed powerful antitumor effects of LN229, and our findings powerfully suggest the possibility of Phen and Met being used as an adjuvant agent in the treatment of glioma patients.

miR-127-5p promotes chondrogenic differentiation in rat bone marrow mesenchymal stem cells.

The effect and related mechanisms of miR-127-5p on the cartilage differentiation of rat bone marrow mesenchymal stem cells (BMSCs) was investigated. Rat BMSCs were generated and transfected with miR-127-5p, RT-PCR and Safranin O staining were used to detect the effect of miR-127-5p on the cartilage differentiation of rat BMSCs. Western blot analysis was used to detect the related mechanisms of miR-127-5p on the cartilage differentiation of rat BMSCs. Genes related to cartilage differentiation such as Sox9, collagen II and aggrecan were significantly increased in the group which were transfected with miR-127-5p, while collagen X, which was related to cartilage hypertrophy, was decreased in the miR-127-5p transfected group. Safranin O staining revealed that the expression of chondroitin sulfate was significantly increased in the group of miR-127-5p, than the miRNA control group. Western blot analysis showed that miR-127-5p transfection promoted the expression of Sox9, while decreased the expression of Runx2 of rat BMSCs. In conclusion, via increasing the expression of Sox9 and decreasing the expression of Runx2, miR-127-5p could promote cartilage differentiation and decrease cartilage hypertrophy of rat BMSCs.

Isolated leukemic infiltration of peripheral nervous system.

INTRODUCTION: Isolated leukemic infiltration of peripheral nerves without central nervous system involvement, or isolated neuroleukemiosis, is an extremely rare complication of leukemia. METHODS: We report the case of a patient with isolated neuroleukemiosis and review the pertinent literature. RESULTS: A man with a 12-year history of acute monoblastic leukemia presented with median mononeuropathy. Magnetic resonance imaging revealed a thickened median nerve. Nerve biopsy confirmed the diagnosis of leukemic infiltration. Clinical resolution was achieved through local radiation. Only 10 cases of isolated neuroleukemiosis have been reported. Most were in remission from leukemia. Our patient is the only one who was considered clinically cured of leukemia. CONCLUSIONS: The presumed pathophysiology of isolated neuroleukemiosis is hematogenous spread of leukemic cells into the peripheral nervous system across the blood-nerve barrier. It should be considered in the differential diagnosis in patients with leukemia who present with neuropathy, even when they are considered to be clinically cured of leukemia.

Tumor-suppressive function of miR-139-5p in esophageal squamous cell carcinoma.

Recent studies have demonstrated the possible function of miR-139-5p in tumorigenesis. However, the exact mechanism of miR-139-5p in cancer remains unclear. In this study, the association of miR-139-5p expression with esophageal squamous cell carcinoma (ESCC) was evaluated in 106 pairs of esophageal cancer and adjacent non-cancerous tissue from ESCC patients. The tumor suppressive features of miR-139-5p were measured by evaluating cell proliferation and cell cycle state, migratory activity and invasion capability, as well as apoptosis. Luciferase reporter assay and Western blot analysis were performed to determine the target gene regulated by miR-139-5p. The mRNA level of NR5A2, the target gene of miR-139-5p, was determined in ESCC patients. Results showed that reduced miR-139-5p level was associated with lymph node metastases of ESCC. MiR-139-5p was investigated to induce cell cycle arrest in the G0/G1 phase and to suppress the invasive capability of esophageal carcinoma cells by targeting the 3'UTR of oncogenic NR5A2. Cyclin E1 and MMP9 were confirmed to participate in cell cycle arrest and invasive suppression induced by NR5A2, respectively. Pearson correlation analysis further confirmed the significantly negative correlation between miR-139-5p and NR5A2 expression. The results suggest that miR-139-5p exerts a growth- and invasiveness-suppressing function in human ESCCs, which demonstrates that miR-139-5p is a potential biomarker for early diagnosis and prognosis and is a therapeutic target for ESCC.

[The clinical therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization in treating primary liver cancer with pulmonary metastases].

OBJECTIVE: To observe the therapeutic effects of arsenic trioxide combined with transcatheter arterial chemoembolization on treatment of primary liver cancer with pulmonary metastases. METHODS: Sixty patients were randomly divided into two groups: group A (treatment group, n = 30) and group B (control group, n = 30). Group A was received periodic transcatheter arterial chemoembolization (TACE) and 10 mg arsenic trioxide by intravenous infusion for 5 hours per day, 3 days after TACE. Each cycle consisted of 14 days' administration, and repeated after 2 weeks. Each patient was received 3-4 successive cycles. Group B was received periodic TACE alone. OBJECTIVE: efficiency, benefit rate, quality of life and the correlates with metastatic tumor size and number in the both groups were recorded. RESULTS: The objective efficiency was 26.7% (8/30), and the benefit rate was 60.0% (18/30) in group A, while they were 0 and 16.7% (5/30) in group B with significant statistics differences (χ(2) = 7.067, P = 0.008; χ(2) = 11.915, P = 0.001). The quality of life was improved in 4 patients and stable in 18 of group A, while no patient was improved and 13 were stable in group B (χ(2) = 9.669, P = 0.008). There was a significantly positive correlation between the tumor burden and therapeutic effect (Kendall r = -0.765, P < 0.001; Spearman r = -0.821, P < 0.001). CONCLUSION: Arsenic trioxide combined TACE is an effective treatment method in treating primary liver cancer with pulmonary metastases.

Survival trends in gastric cancer patients of Northeast China.

AIM: To describe survival trends in patients in Northeast China diagnosed as gastric cancer. METHODS: A review of all inpatient and outpatient records of gastric cancer patients was conducted in the First Affiliated Hospital of China Medical University. All the gastric cancer patients who satisfied the inclusion criteria from January 1, 1980 through December 31, 2003 were included in the study. The main outcomes were based on median survival and 3-year and 5-year survival rates, by decade of diagnosis. RESULTS: From 1980 through 2003, the median survival for patients with gastric cancer (n = 1604) increased from 33 mo to 49 mo. The decade of diagnosis was not significantly associated with patient survival for gastric cancer (P = 0.084 for overall survival, and P = 0.150 for 5-year survival); however, the survival rate of the 2000s was remarkably higher than that of the 1980s (P = 0.019 for overall survival, and P = 0.027 for 5-year survival). CONCLUSION: There was no significant difference of survival among each period; however, the survival rate of the 2000s was remarkably higher than that of the 1980s.

[Levels of P27Kip1 expression and apoptosis in HL-60 cells after treatment with TGF-ß1 and/or arsenic trioxide].

This study was purposed to investigate the effects of TGF-beta1 and arsenic trioxide (As2O3) on cell apoptosis, cell cycle and changes of P27(Kip1), endogenous TGF-ß1, cyclin E and BCL-2 in HL-60 cells, and to explore the relationship between expression of P27(Kip1) and apoptosis induced by As2O3 and/or TGFß1. Cell apoptosis and cell cycle changes of HL-60 cells treated with As2O3 and/or TGFß1 were detected by cytomorphologic observation and flow cytometry, the protein expressions of P27(Kip1), TGF-ß1, cyclin E and BCL-2 were measured by immunohistochemistry. The results showed the effect of 5 µmol/L of As2O3 was the most strong among the different concentration of As2O3 ,and the effect on apoptosis at 48 hour was more strong than that at 24 hours (p < 0.05). The TGF-beta1 (5 ng/ml) induced arrest of cells in G1 phase (p < 0.05) compared with As2O3 alone and As2O3 combined with TGF-ß1, while there was no difference with control. P27(Kip1) expression was up regulated (p < 0.05), cyclin E and BCL-2 expression was down-regulated (p < 0.05) in TGFß1-treated group. BCl-2 expression was down regulated, endogenesis TGFß1 expression was up regulated (p < 0.05), and the level of P27(kip1) and cyclin E were not changed in As2O3-treated group (p > 0.05). The down-regulating effect of TGF-ß1 combined with As2O3 on BCL-2 protein was more strong than that in single factor treated group (p < 0.05). It is concluded that TGFß1 induces cell cycle arrest and apoptosis in HL-60 cells, while the P27(kip1) expression is up regulated. P27 protein is the key effector of TGFß-induced cell cycle arrest. The effect of TGF-ß1 combined with As2O3 on apoptosis as well as the down-regulation of BCL-2 protein in HL-60 cells is more strong than that in single factor-treated groups, that indicates the passages linking up each other.