Oleandrin synergizes with cisplatin in human osteosarcoma cells by enhancing cell apoptosis through activation of the p38 MAPK signaling pathway.


PURPOSE:Our previous studies have reported the antitumor effect of oleandrin on osteosarcoma; however, its chemosensitizing effect in osteosarcoma treatment is still unknown. Therefore, we explored the sensitizing effects of oleandrin to cisplatin in osteosarcoma and investigated the potential mechanisms. METHODS:After exposure to oleandrin and/or cisplatin, CCK-8 and colony formation assays, DAPI staining and flow cytometry were performed to detect cell proliferation and apoptosis in 143B, U-2OS and MG-63 osteosarcoma cells. The median-effect analysis was applied to evaluate the combined effect. Western blot was used to determine the expression of related proteins. Osteosarcoma xenografts and histological observations were applied to confirm the combined effect in vivo. RESULTS:Compared with cisplatin or oleandrin alone, the combined treatment significantly inhibited cell proliferation and induced cell apoptosis. The median-effect analysis indicated a synergistic cytotoxic effect. The combined treatment downregulated Bcl-2 and upregulated Bax and cleaved caspase-3, -8 and -9. And the suppression of caspases reduced cell death. Furthermore, oleandrin alone or with cisplatin, activated the p38 MAPK/Elk-1 pathway. The inhibition of the p38 MAPK pathway increased cell viability and reduced apoptosis. In vivo, the combined treatment was also verified to significantly inhibit tumor growth, induce apoptosis and activate the p38 MAPK pathway. CONCLUSIONS:The combination of oleandrin with cisplatin exerts a synergistic antitumor effect in osteosarcoma, which relates to the activation of the p38 MAPK pathway.


Yong L,Ma Y,Zhu B,Liu X,Wang P,Liang C,He G,Zhao Z,Liu Z,Liu X




Has Abstract


2018-12-01 00:00:00














  • Clinical pharmacology of intracarotid etoposide.

    abstract::Pharmacokinetics studies were performed in ten patients who received VP-16 by intracarotid infusion at 100-300 mg/m2. VP-16 was analyzed by high-pressure liquid chromatography. ESTRIP and NONLIN were used to characterize VP-16 pharmacokinetics. VP-16 disappeared biphasically, with a t1/2 beta of 6.1 +/- 1.4 h; the tot...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Savaraj N,Feun LG,Lu K,Wallace S,Fields WS,Loo TL

    更新日期:1986-01-01 00:00:00

  • Tumor resensitization to erlotinib following brief substitution of cetuximab.

    abstract::Targeted inhibition of epidermal growth factor receptors (EGFR) is becoming a standard anticancer treatment in defined clinical scenarios. EGFR inhibition may be achieved either by small-molecule orally bioavailable tyrosine kinase inhibitors, such as gefitinib or erlotinib, or else by large-molecule receptor antibodi...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Epstein RJ,Leung TW

    更新日期:2008-11-01 00:00:00

  • 2-Methoxyestradiol inhibits hepatocellular carcinoma cell growth by inhibiting Cdc25 and inducing cell cycle arrest and apoptosis.

    abstract:PURPOSE:2-Methoxyestradiol (2-ME) is a physiological metabolite of estrogen, which can inhibit growth of many types of tumor cells, including hepatocellular carcinoma, both in vitro and in vivo. The exact mechanisms of its action are still unclear. We have studied the mechanisms of growth inhibition of several of human...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kar S,Wang M,Carr BI

    更新日期:2008-10-01 00:00:00

  • Cytoprotective and regulatory functions of glutathione S-transferases in cancer cell proliferation and cell death.

    abstract:PURPOSE:Glutathione S-transferases (GSTs) family of enzymes is best known for their cytoprotective role and their involvement in the development of anticancer drug resistance. Recently, emergence of non-detoxifying properties of GSTs has provided them with significant biological importance. Addressing the complex inter...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审


    authors: Singh S

    更新日期:2015-01-01 00:00:00

  • Pharmacokinetics of 5-fluorouracil infusions in the rat: comparison with man and other species.

    abstract::Saturable elimination of 5-FU is exhibited in rats during constant infusions. Over the range of 3-480 mg/m2/h, total-body clearance of 5-FU decreases from 600 ml/min/m2 to less than 90 ml/min/m2. Previously published values for catabolism of 5-FU by rat hepatocytes can be used to simulate the plasma concentrations of ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Collins JM

    更新日期:1985-01-01 00:00:00

  • Physicochemical and pharmacokinetic parameters of seven lipophilic chlorambucil esters designed for brain penetration.

    abstract::This report describes the physicochemical and pharmacokinetic parameters of seven chlorambucil esters, which were compared with those of chlorambucil. These esters were designed as chlorambucil prodrugs to increase the brain penetration and concentration vs time profile of chlorambucil within the CNS for potential tre...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Greig NH,Genka S,Daly EM,Sweeney DJ,Rapoport SI

    更新日期:1990-01-01 00:00:00

  • Inhibition of glutathione synthesis reverses Krüppel-like factor 4-mediated cisplatin resistance.

    abstract:PURPOSE:To explore the protective effect of KLF4 against cytotoxicity induced by cisplatin and its possible mechanisms. METHODS:The expression levels of KLF4 were detected by RT-PCR and western blot in cancer stem-like cells derived from hepatocarcinoma (T3A-A3) and the hepatocarcinoma cell line HepG2. KLF4 was knocke...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Jia Y,Zhang W,Liu H,Peng L,Yang Z,Lou J

    更新日期:2012-02-01 00:00:00

  • D-dimer increase: an unfavorable factor for patients with primary liver cancer treated with TACE.

    abstract:PURPOSE:To explore the clinical significance of plasma D-dimer increase for transcatheter arterial chemoembolization (TACE) in patients with primary liver cancer (PLC). METHODS:The clinical data of 80 PLC patients who underwent TACE in our hospital from January 2015 to January 2017 were collected, including the plasma...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Chen X,Chang Z,Liu Z

    更新日期:2019-04-01 00:00:00

  • Population pharmacokinetics of pemetrexed disodium (ALIMTA) in patients with cancer.

    abstract:PURPOSE:To evaluate the population pharmacokinetics of pemetrexed disodium in cancer patients enrolled in four different open-label, multicenter, nonrandomized phase II studies. METHODS:Pemetrexed disodium was administered as a 10-min intravenous infusion (600 mg/m2) every 21 days. A total of four blood samples were t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Ouellet D,Periclou AP,Johnson RD,Woodworth JR,Lalonde RL

    更新日期:2000-01-01 00:00:00

  • Reversal of multidrug resistance in Friend leukemia cells by dexniguldipine-HCl.

    abstract::Dexniguldipine-HCl (DNIG)--a prospective clinical modulator of p170-glycoprotein (pgp170)-mediated multidrug resistance (MDR)--was evaluated in a drug-accumulation assay in MDR murine leukemia cell strain F4-6RADR expressing pgp170. The compound elevated low accumulation of either doxorubicin (DOX), daunorubicin (DNR)...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Reymann A,Looft G,Woermann C,Dietel M,Erttmann R

    更新日期:1993-01-01 00:00:00

  • Phase I study of combination therapy with weekly paclitaxel and cyclophosphamide for advanced or recurrent breast cancer.

    abstract:PURPOSE:Although anthracycline is a key agent in breast cancer treatment, its use is associated with the risk of cardiotoxicity. Recently, the value of combination therapy with docetaxel and cyclophosphamide was reported. Because the characteristics of paclitaxel differ on weekly versus tri-weekly administration, such ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Masuda N,Nakayama T,Yamamura J,Kamigaki S,Taguchi T,Hatta M,Sakamoto J

    更新日期:2010-05-01 00:00:00

  • The role of comparative pharmacokinetics in the planning of human dose escalation: the experience with diacetyldianhydrogalactitol.

    abstract::The pharmacokinetics of diacetyldianhydrogalactitol (DADAG) was compared in mice, rats, and humans. The ratios of human therapeutic dose (ThD) to the LD10 were 8 and 5 in mice and rats, respectively. The ratios of the corresponding AUCs of DADAG were 20 and 17, whereas those of dianhydrogalactitol (DAG), the main, act...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kerpel-Fronius S,Erdélyi-Tóth V,Somfai-Relle S,Csetényi J,Kovács P,Ujj G,Kanyár B

    更新日期:1988-01-01 00:00:00

  • Angiostatin potentiates cyclophosphamide treatment of metastatic disease.

    abstract:PURPOSE:We examined the interaction between cyclophosphamide (CPA) and angiostatin (AS) on the growth of primary Lewis lung carcinoma (LLC) tumors and on the development of LLC pulmonary metastases. We studied the effects of AS and CPA on the stages of angiogenesis employing in vitro assays. METHODS:Primary tumor grow...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Mauceri HJ,Seetharam S,Beckett MA,Schumm LP,Koons A,Gupta VK,Park JO,Manan A,Lee JY,Montag AG,Kufe DW,Weichselbaum RR

    更新日期:2002-11-01 00:00:00

  • Modulation of adriamycin cytotoxicity and transport in drug-sensitive and multidrug-resistant Chinese hamster ovary cells by hyperthermia and cyclosporin A.

    abstract:PURPOSE:Chemosensitizers such as cyclosporin A can increase intracellular accumulation of chemotherapeutic agents such as Adriamycin in certain multidrug-resistant (MDR) cell lines with overexpression of P-glycoprotein. It is likely that, when combined with cyclosporin A, hyperthermia could increase membrane permeabili...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Larrivée B,Averill DA

    更新日期:2000-01-01 00:00:00

  • Reduced dose pegfilgrastim is associated with less bone pain without increased neutropenia: a retrospective study.

    abstract:BACKGROUND:Chemotherapy for breast cancer is associated with a high risk of neutropenia. Pegfilgrastim reduces the risk of neutropenic fever but commonly causes bone pain. OBJECTIVE:Evaluate whether a reduced dose of pegfilgrastim (3 mg) reduced the frequency of bone pain without compromising efficacy. METHODS:Record...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Lower EE,Charif M,Bartelt M

    更新日期:2018-07-01 00:00:00

  • Biweekly docetaxel, cisplatin, and 5-fluorouracil (DCF) chemotherapy for advanced esophageal squamous cell carcinoma: a phase I dose-escalation study.

    abstract:BACKGROUND AND PURPOSE:The optimal chemotherapeutic protocol for the treatment of esophageal cancer has not yet been established. A dose-escalation study of docetaxel combined with cisplatin and 5-fluorouracil (5-FU) was performed to determine the optimal dose in patients with advanced esophageal squamous cell carcinom...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Tanaka Y,Yoshida K,Sanada Y,Osada S,Yamaguchi K,Takahashi T

    更新日期:2010-11-01 00:00:00

  • Initial clinical experience with a simultaneous combination of 2,4-diamino-5(3',4'-dichlorophenyl)-6-methylpyrimidine (DDMP) with folinic acid.

    abstract::DDMP, a diaminopyrimidine folate antagonist, was given to 26 tumor patients in a dosage of 50 mg/m2 per week orally, simultaneously with 3 mg CF i.m. or i.v. The CF dose was increased to 30 mg in patients showing evidence of toxicity, and withdrawn in the absence of toxicity. The dose-limiting toxicity was seen in mye...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Alberto P,Peytremann R,Medenica R,Beretta-Piccoli M

    更新日期:1978-01-01 00:00:00

  • Effects of posaconazole (a strong CYP3A4 inhibitor), two new tablet formulations, and food on the pharmacokinetics of idasanutlin, an MDM2 antagonist, in patients with advanced solid tumors.

    abstract:PURPOSE:Idasanutlin, a selective small-molecule MDM2 antagonist in phase 3 testing for refractory/relapsed AML, is a non-genotoxic oral p53 activator. To optimize its dosing conditions, a number of clinical pharmacology characteristics were examined in this multi-center trial in patients with advanced solid tumors. ME...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Nemunaitis J,Young A,Ejadi S,Miller W,Chen LC,Nichols G,Blotner S,Vazvaei F,Zhi J,Razak A

    更新日期:2018-03-01 00:00:00

  • Doxorubicin and doxorubicinol plasma concentrations and excretion in parotid saliva.

    abstract::The pharmacokinetics of doxorubicin (DOX) and doxorubicinol (DOXol) was studied in six patients with various advanced neoplastic diseases who received 28-72 mg/m2 DOX (nine courses). Plasma and parotid saliva were collected over a 48-h period, and DOX and DOXol were quantified by high-performance liquid chromatography...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Bressolle F,Jacquet JM,Galtier M,Jourdan J,Donadio D,Rossi JF

    更新日期:1992-01-01 00:00:00

  • Formulation of a triple combination gemcitabine plus romidepsin + cisplatin regimen to efficaciously and safely control triple-negative breast cancer tumor development.

    abstract:PURPOSE:Triple-negative breast cancer (TNBC) is an aggressive, lethal, and heterogeneous subtype of breast cancers, tending to have lower 5-year survival rates than other BC subtypes in response to conventional chemotherapies. This study's aim was to identify advanced regimens to effectively control TNBC tumor developm...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Pattarawat P,Wallace S,Pfisterer B,Odoi A,Wang HR

    更新日期:2020-01-01 00:00:00

  • High-dose epirubicin as primary chemotherapy in advanced breast carcinoma: a phase II study.

    abstract::A total of 40 patients with metastatic breast cancer were treated with 120 mg/m2 i.v. epirubicin every 3 weeks for a maximum of 10 cycles. Nine achieved a complete response and 17 showed a partial response, for an objective response rate of 65% (95% confidence interval, 47%-83%); the median duration of response was 7 ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Carmo-Pereira J,Costa FO,Miles DW,Henriques E,Richards MA,Rubens RD

    更新日期:1991-01-01 00:00:00

  • Preclinical pharmacokinetics and oral bioavailability of BMS-310705, a novel epothilone B analog.

    abstract:PURPOSE:BMS-310705, a novel semisynthetic derivative of epothilone B, is a tubulin-polymerization agent currently in phase I clinical trials for anticancer therapy. The in vitro and in vivo pharmacokinetics and oral bioavailability of BMS-310705 were investigated in mice, rats, and dogs. In addition, comparison of the ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Kamath AV,Chang M,Lee FY,Zhang Y,Marathe PH

    更新日期:2005-08-01 00:00:00

  • Doxorubicin binds in a cooperative manner to myocardial cells. Two binding sites.

    abstract::Experimental evidence indicates that the anthracycline antibiotic doxorubicin (adriamycin) localizes mainly in cell nuclei of cardiac cells and has a high affinity to several cellular constituents in addition to DNA. In the present study the cellular kinetics of doxorubicin in cultured rat myocardial cells were determ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Wassermann K,Steiness E

    更新日期:1986-01-01 00:00:00

  • Clinical effects and pharmacokinetics of the fusion protein PIXY321 in children receiving myelosuppressive chemotherapy.

    abstract:UNLABELLED:A hemopoietin with the ability to accelerate both platelet and granulocyte recovery after intensive chemotherapy would have great clinical utility. The recombinant fusion protein composed of human granulocyte-macrophage colony-stimulating factor and interleukin-3 (PIXY321), showed some promise in early adult...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Furman WL,Rodman JH,Tonda ME,Luo X,Arnold B,Marina N,Garrison L,Hanna R,Pratt CB,Meyer WH

    更新日期:1998-01-01 00:00:00

  • Phase I study of veliparib in combination with gemcitabine.

    abstract:BACKGROUND:Veliparib (ABT-888) is an oral PARP inhibitor expected to increase gemcitabine activity. This phase I determined the maximal tolerable dose (MTD), dose-limiting toxicities (DLT), antitumor activity, pharmacokinetics (PK), and pharmacodynamics (PD) of veliparib combined with gemcitabine. METHODS:Patients wit...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,多中心研究


    authors: Stoller R,Schmitz JC,Ding F,Puhalla S,Belani CP,Appleman L,Lin Y,Jiang Y,Almokadem S,Petro D,Holleran J,Kiesel BF,Ken Czambel R,Carneiro BA,Kontopodis E,Hershberger PA,Rachid M,Chen A,Chu E,Beumer JH

    更新日期:2017-09-01 00:00:00

  • Phase I-II study of the somatostatin analogue lanreotide in hormone-refractory prostate cancer.

    abstract::Lanreotide (BIM 32014), a somatulin analogue, was found to be as effective as castration in a rat prostate tumor model. Therapeutic benefit was also demonstrated in the hormone-resistant phase of this tumor model. The activity of lanreotide may be due to a reduction in the levels of growth factors such as insulin grow...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Maulard C,Richaud P,Droz JP,Jessueld D,Dufour-Esquerré F,Housset M

    更新日期:1995-01-01 00:00:00

  • Biweekly oxaliplatin plus 1-day infusional fluorouracil/leucovorin followed by metronomic chemotherapy with tegafur/uracil in pretreated metastatic colorectal cancer.

    abstract:PURPOSE:Metronomic chemotherapy, at a minimally toxic dose and with a frequent schedule, is a potentially novel approach to the control of advanced cancer disease via a different mechanism from maximum tolerable doses chemotherapy. Taking advantage of the potential effectiveness of metronomic therapy, tegafur/uracil (U...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 临床试验,杂志文章


    authors: Lin PC,Chen WS,Chao TC,Yang SH,Tiu CM,Liu JH

    更新日期:2007-08-01 00:00:00

  • Should EGFR mutations be tested in advanced lung squamous cell carcinomas to guide frontline treatment?

    abstract::There is no argument over using epidermal growth factor receptor (EGFR) mutation status to guide the frontline treatment for advanced lung adenocarcinoma (LADC); however, the role of the testing in lung squamous cell carcinoma (LSQC) remains controversial. Currently, the guidelines/consensus statements regarding EGFR ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章,评审


    authors: Chiu CH,Chou TY,Chiang CL,Tsai CM

    更新日期:2014-10-01 00:00:00

  • Inhibition of thymidylate synthase by the diastereoisomers of leucovorin.

    abstract::The clinical formulation of leucovorin (5-CHO-FH4) is a mixture of diastereoisomers with markedly different pharmacologic properties. Comparatively little information is available concerning the cellular pharmacology of reduced folate stereoisomers, due largely to the difficulty in preparing sufficient quantities of t...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 杂志文章


    authors: Lee PP,Schilsky RL

    更新日期:1990-01-01 00:00:00

  • MDA-MB-435 cells are from melanoma, not from breast cancer.

    abstract::For years, MDA-MB-435 cells have been widely but erroneously used as breast cancer cells with aggressive behaviour. Recent data show that they are in fact melanoma cells. However, many scientists are still unaware of this "new" identity. ...

    journal_title:Cancer chemotherapy and pharmacology

    pub_type: 评论,信件


    authors: Lacroix M

    更新日期:2009-02-01 00:00:00