Abstract:
PURPOSE:This study aimed at investigating the anti-tumor effect of arsenic sulfide (As2S2) against liver cancer both in vivo and in vitro and to elucidate its underlying mechanisms. METHODS:Cell viability of the human hepatocellular carcinoma cell lines SMMC-7721, BEL-7402, HepG2 were measured by CCK-8 assay. The effects of As2S2 on cell proliferation and apoptosis of SMMC-7721 cells were investigated using Calcein-AM and PI staining, Hoechst 33258 staining, crystal violet staining, and JC-1 staining. Cell cycle and Annexin V/PI assay were analyzed via flow cytometry. The expression of apoptosis-related proteins, phosphorylation of PI3K and AKT were detected by Western blotting. H22-bearing mice model was established to evaluate the anti-tumor effect of As2S2 in vivo. HE staining, PCNA was observed via immunohistochemistry, and TUNEL assay was used to assess the anti-proliferation and pro-apoptotic effects of As2S2. RESULTS:As2S2 significantly inhibited the growth of human hepatoma cells SMMC-7721, BEL-7402 and HepG2. As2S2 inhibited cell proliferation effectively by inducing G0/G1 cell cycle arrest in SMMC-7721 cells. As2S2 could increase Bax/Bcl-2 ratio, decrease mitochondrial membrane potential, promote the release of cytochrome c, increase the levels of cleaved caspase-3 and PARP, indicating that As2S2 induced apoptosis in SMMC-7721 cells via mitochondrial-mediated apoptosis pathway. Further research showed that As2S2 inhibited the PI3K/AKT signaling pathway leading to apoptotic cell death. In addition, As2S2 significantly inhibited tumor growth in H22-bearing mice and induced apoptosis by deactivating PI3K/AKT pathway, which was consistent with the in vitro results. CONCLUSION:These findings suggested that As2S2 could induce apoptosis of liver cancer cells in vitro and in vivo, which was related to PI3K/AKT-mediated mitochondrial pathway and may provide a novel promising therapeutic agent for liver cancer treatment.
journal_name
Cancer Chemother Pharmacoljournal_title
Cancer chemotherapy and pharmacologyauthors
Wang S,Zhang C,Li Y,Li P,Zhang D,Li Cdoi
10.1007/s00280-018-3755-9subject
Has Abstractpub_date
2019-03-01 00:00:00pages
519-530issue
3eissn
0344-5704issn
1432-0843pii
10.1007/s00280-018-3755-9journal_volume
83pub_type
杂志文章abstract:PURPOSE:In clinical trials, the epidermal growth factor receptor tyrosine kinase inhibitor (EGFR-TKI) administered concomitantly with first-line cytotoxicity chemotherapy failed to confer a survival benefit to patients with non-small-cell lung cancer (NSCLC). The aim of this study was to test whether paclitaxel followe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-010-1347-4
更新日期:2011-03-01 00:00:00
abstract:OBJECTIVES:To assess the cardiovascular safety, tolerability and efficacy of high doses of granisetron for the treatment of nausea and vomiting in patients undergoing highly emetogenic chemotherapy. METHODS:Patients with histologically confirmed malignant disease were given an intravenous infusion of granisetron, 160 ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-003-0689-6
更新日期:2004-02-01 00:00:00
abstract::Etoposide has demonstrated highly significant clinical activity against a wide variety of neoplasms, including germ-cell malignancies, small-cell lung cancer, non-Hodgkin's lymphomas, leukemias, Kaposi's sarcoma, neuroblastoma, and soft-tissue sarcomas. It is also one of the important agents in the preparatory regimen...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/BF00684875
更新日期:1994-01-01 00:00:00
abstract:PURPOSE:D-Limonene is a natural monoterpene with pronounced chemotherapeutic activity and minimal toxicity in preclinical studies. A phase I clinical trial to assess toxicity, the maximum tolerated dose (MTD) and pharmacokinetics in patients with advanced cancer was followed by a limited phase II evaluation in breast c...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050793
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:To assess the potential for drug-drug interactions between lenalidomide and substrates and inhibitors of cytochrome P450 (CYP) isozymes. METHODS:In vitro metabolism of lenalidomide by human liver microsomes, recombinant human CYPs and human hepatocytes was evaluated. The inhibitory and inductive effects of len...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-008-0867-7
更新日期:2009-05-01 00:00:00
abstract:PURPOSE:The combination of capecitabine and paclitaxel (XP) has demonstrated synergistic antitumor activity in preclinical models. The purpose of this phase II study was to evaluate the efficacy and safety of a monthly XP regimen in patients with metastatic breast cancer (MBC). METHODS:Eligible patients had received o...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,多中心研究
doi:10.1007/s00280-012-2068-7
更新日期:2013-03-01 00:00:00
abstract::In recent years significant progress in the understanding of the immune biology of melanoma has evolved from the identification of melanoma antigens (MAs) recognized by T cells. MAs consist of intracellular proteins that are expressed on the surface of cancer cells in association with human leukocyte antigen (HLA) cla...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,评审
doi:10.1007/pl00014052
更新日期:2000-01-01 00:00:00
abstract:PURPOSE:The objectives of this phase I dose-finding study of erlotinib were to investigate the toxicity profile, to confirm the acceptable toxicity of doses up to 150 mg/day, and to assess the pharmacokinetic (PK) profile and antitumor activity in Japanese patients with solid tumors. PATIENTS AND METHODS:Patients with...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-007-0494-8
更新日期:2008-03-01 00:00:00
abstract:UNLABELLED:Hypericin, a polycyclic aromatic dianthroquinone, is a natural pigment derived from the plant Hypericum perforatum (St John's Wort). The compound has been synthesized and shown to inhibit the growth of malignant glioma cell lines in vitro via inhibition of protein kinase C. Oral hypericin has entered clinica...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800000188
更新日期:2001-01-01 00:00:00
abstract::We studied bioavailability, treatment schedule dependence, and therapeutic efficacy of orally administered MST-16, a novel derivative of bis(2,6-dioxopiperazine), against murine tumors and human tumor xenografts. The rate of its intestinal absorption was about 50%, and it was immediately metabolized to its parent comp...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685528
更新日期:1991-01-01 00:00:00
abstract::Infusion of 5'-dFUrd (2.0-3.0 g/m2 over 1 h on days 1-5 every 3rd week) resulted in one partial response in 21 patients with advanced and progressing colorectal cancer. No patient had received chemotherapy before the 5'-dFUrd trial. Hematological and gastrointestinal toxicity were generally mild. In 4 patients periphe...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257528
更新日期:1985-01-01 00:00:00
abstract::Imidazoacridinones are a new class of highly potent antineoplastic agents synthesised at the Technical University of Gdansk. The pharmacophoric alkyldiamine group, which is also present in anthracenediones (e.g. ametantrone, mitoxantrone), has been shown to be responsible for their antineoplastic activity. In view of ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s002800050445
更新日期:1996-01-01 00:00:00
abstract:PURPOSE:In order to determine the sensitivity and specificity of the test and to optimize experimental conditions utilizing the SBT in a rat model of chemotherapy-induced small intestinal damage. METHODS:Initially, a 13C-sucrose dose-response study was performed in rats to determine an optimal sucrose concentration fo...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-1098-2
更新日期:2010-04-01 00:00:00
abstract::Eighteen previously untreated patients with advanced unresectable or metastatic soft-tissue sarcomas (STS) and two patients with locally invasive thymoma were treated with a combination of adriamycin (ADM) 80 mg/m2 on day 1 and cis-platinum (DDP) 120 mg/m2 on day 1. The regimen was repeated at 4-weeks intervals. In ST...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00257118
更新日期:1984-01-01 00:00:00
abstract:PURPOSE:Bevacizumab (BV) prolongs the survival of colorectal cancer patients when combined with irinotecan (CPT-11)-based regimens. In the AVF2107g study, the area under the curve (AUC) ratio for bolus CPT-11/5-fluorouracil (5-FU)/leucovorin (LV) (IFL) with the BV arm to bolus IFL with placebo indicated that SN-38 conc...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s00280-009-1051-4
更新日期:2010-02-01 00:00:00
abstract::Sodium cyanate (NaOCN) at a dose of 250 mg/kg was shown to decrease protein synthesis in P388 leukemia tumor cells to approximately 52% of control values at 2 h and 32% at 5 h after NaOCN administration, without a corresponding decrease in various normal tissues of the tumor-bearing CD2Fl mice. CD2Fl mice that had rec...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00254597
更新日期:1984-01-01 00:00:00
abstract::Isothiocyanate sulforaphane (SFN) is a potent cancer chemopreventive agent. We investigated the mechanisms underlying the anti-proliferative effects of SFN in the human colon carcinoma cell line, HT-29. We demonstrate that SFN inhibits the growth of HT-29 cells in a dose- and time-dependent manner. Treatment of serum-...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-005-0050-3
更新日期:2006-02-01 00:00:00
abstract::We evaluated the stability of the aqueous formulation of mesna during storage in syringes and after dilution in beverages and syrups. Measurements of the concentrations of mesna showed that the undiluted formulation was stable for at least 9 days in standard polypropylene syringes at 5 degrees, 24 degrees, and 35 degr...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00685538
更新日期:1991-01-01 00:00:00
abstract:PURPOSE:Capecitabine and S-1 are orally administered fluoropyrimidine anticancer drugs widely used to treat gastrointestinal cancer. While anticoagulant therapy for cancer patients is recommended, many studies have shown that the effects of warfarin are enhanced by its interaction with fluoropyrimidine. We investigated...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3080-0
更新日期:2016-08-01 00:00:00
abstract::Schedule dependency of bisantrene was evaluated in refractory metastatic breast cancer. Patients were randomly assigned to receive either a single (S) bolus injection of 300 mg/m2 (37 patients) or an injection of 80 mg/m2 daily for 5 days (D x 5) (35 patients) every 3-4 weeks after stratification by performance status...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,随机对照试验
doi:10.1007/BF00262287
更新日期:1986-01-01 00:00:00
abstract:PURPOSE:The purpose of this investigation was to synthesize a series of carbonate and carbamate derivatives of 4-demethylpenclomedine (DM-PEN), the major plasma non-toxic metabolite of penclomedine (PEN) seen in patients. DM-PEN has been observed to be an active antitumor agent in mouse human xenograft tumor models and...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0933-9
更新日期:2009-09-01 00:00:00
abstract::We studied serum lipid and lipoprotein changes occurring during chemotherapy in 57 patients with chemosensitive cancers, including 18 malignant lymphomas, 18 breast carcinomas, 14 small-cell lung carcinomas, and 7 urothelial-cell carcinomas. Patients who responded favorably to chemotherapy demonstrated a significant i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689971
更新日期:1992-01-01 00:00:00
abstract:PURPOSE:To assess the effect of elotuzumab on corrected QT (QTc) intervals and cardiac safety. METHODS:Patients with high-risk smoldering multiple myeloma who had been treated with elotuzumab monotherapy (10 or 20 mg/kg) in Study CA204011 (NCT01441973) underwent electrocardiogram (ECG) examination over 8-10 weeks (tre...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-016-3182-8
更新日期:2016-12-01 00:00:00
abstract:PURPOSE:Neoadjuvant CT-P6, a trastuzumab biosimilar, demonstrated equivalent efficacy to reference trastuzumab in a phase 3 trial of HER2-positive early-stage breast cancer (EBC) (NCT02162667). We report post hoc analyses evaluating pathological complete response (pCR) and breast pCR alongside additional efficacy and s...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章,随机对照试验
doi:10.1007/s00280-019-03920-4
更新日期:2019-10-01 00:00:00
abstract:PURPOSE:To investigate the effect of granulocyte colony-stimulating factor (G-CSF) on the pharmacokinetics and pharmacodynamics of the new morpholino anthracycline drug MX2. METHODS:A total of 25 patients with advanced malignant disease participated in a dose-escalation study in the first cycle of treatment given i.v....
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章
doi:10.1007/s002800050761
更新日期:1998-01-01 00:00:00
abstract:PURPOSE:The histone deacetylase inhibitor, suberoylanilide hydroxamic acid (SAHA), enhances cisplatin [cis-diammine dichloroplatinum (II)] (CDDP)-induced apoptosis in the oral squamous cell carcinoma (OSCC) cell line by complex, multifunctional mechanisms. We investigated the role of endoplasmic reticulum (ER) stress i...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-009-0969-x
更新日期:2009-11-01 00:00:00
abstract::A total of 13 patients receiving bone marrow transplants (BMT) for treatment of different haematological diseases were investigated. Conditioning therapy preceding BMT consisted of fractionated total-body irradiation (12 Gy) and high-dose chemotherapy with cyclophosphamide (2 +/- 60 mg/kg). Patients stratified to be a...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00689585
更新日期:1989-01-01 00:00:00
abstract:PURPOSE:We report the unexpected absence of early relapse (before 30 months) in 24 consecutive patients with isolated limb primary Ewing sarcoma treated with an intensified pilot protocol, SCMCIE94. METHODS:Clinical data for the study were collected retrospectively from the patient files. The protocol included 6 cours...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/s00280-019-03789-3
更新日期:2019-05-01 00:00:00
abstract:INTRODUCTION:Despite the extensive clinical experience with irinotecan, significant concerns remain regarding its toxicity. In a phase I trial, we modulated irinotecan pharmacokinetics by inhibiting biliary excretion of SN-38, the active metabolite of irinotecan, using cyclosporine. The modulation appeared to decrease ...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 临床试验,杂志文章,多中心研究
doi:10.1007/s00280-005-1020-5
更新日期:2005-10-01 00:00:00
abstract::Mitoxantrone, 1,4-dihydroxy-5,8-bis(((2-[(2-hydroxyethyl)amino]ethyl) amino))-9,10-anthracenedione dihydrochloride, a new antitumor agent was evaluated in nine cancer patients as part of a phase I trial. In general, the drug was well tolerated. Leukopenia was the dose-limiting toxic effect. Mild to moderate leukopenia...
journal_title:Cancer chemotherapy and pharmacology
pub_type: 杂志文章
doi:10.1007/BF00578556
更新日期:1980-01-01 00:00:00