Study of the effect of Thioridazine combined with Loratadine on the gastrointestinal tumor suppressor
ZHANG Jin-mei1 KANG Wen-quan1 JIN Guang-yi2 CHEN Ting-ting2,3▲
1.Department of Gastroenterology,Nanshan District People′s Hospital of Shenzhen,Guangdong Province,Shenzhen 518052, China;
2.Department of Pharmacy,School of Medicine,Shenzhen University,Guangdong Province,Shenzhen 518060,China;
3.Department of Cardiology,Shenzhen People′s Hospital(the Second Clinical Medical College of Jinan University), Guangdong Province,Shenzhen 518020,China
Abstract:ObjectiveTo discuss the preliminary effect of nervous system drugs on gastrointestinal tumors.MethodsThioridazine,Loratadine,Scopolamine,Dopamine,Acetylcholine and Estazolamum(0.01,0.1,1,10,100 μmol/L),six classical nervous system drugs were selected to detect the activities of gastrointestinal tumor in vitro by using CCK-8 assay.The spleen cells of mice were also used as the model to study the safety of the nervous system drugs in vitro.ResultsAmong six classical nervous system drugs,cell growth on human colon and gastric cancer clells were suppressed by 100 μmol/L scopolamine,100 μmol/L Loratadine and 10 μmol/L Thioridazine (P<0.05),especially the combination of Thioridazine and Loratadine.Six drugs only played roles in killing tumors cells,while the spleen lymphocytes of normal mice were non-toxic.The growth of mouse gastrointestinal carcinoma cells in vitro were inhibited by 10 μmol/L thioridazine and 25 μmol/L Loratadine.ConclusionThioridazine combined with Loratadine is proved to enhance anti-gastrointestinal tumor effects in vitro,and provides a new strategy for forward combination treatment.
张金梅;康文全;靳广毅;陈婷婷. 硫利达嗪联合氯雷他定抑制胃肠道肿瘤作用的研究[J]. 中国当代医药, 2017, 24(12): 4-8.
ZHANG Jin-mei;KANG Wen-quan;JIN Guang-yi;CHEN Ting-ting. Study of the effect of Thioridazine combined with Loratadine on the gastrointestinal tumor suppressor. 中国当代医药, 2017, 24(12): 4-8.
Masters GA,Krilov L,Bailey HH,et al.Clinical Cancer Advances 2015:annual report on progress against cancer from the American Society of Clinical Oncology[M].J Clin Oncol,2015.
[3]
Eisenhofer G,Aneman A,Friberg P,et al.Substantial production of dopamine in the human gastrointestinal tract[J].J Clin Endocrinol Metab,1997,82(11):3864-3871.
[4]
Beaulieu JM,Gainetdinoy RR.The physiology,signaling,and pharmacology of dopamine receptos[J].Pharmacol Rev,2011,63(1):182-217.
[5]
Chakroborty D,Sarkar C,Mitra Rb,et al.Depleted dopamine in gastric cancer tissues:dopamine treatment retards growth ofgastriccancerbyinhibitingangiogenesis[J].ClinCancerRes,2004,10(13):4349-4356.
Sarker C,Chakroborty D,Chowdhury UR,et al.Dopamine increases the efficacy of anticancer drugs in breast and colon cancer preclinical models[J].Clin Cancer Res,2008,14(8):2502-2510.
[10]
Saha B,Mondal AC,Basu S,et al.Circulating dopamine level,in lung carcinoma patients,inhibits proliferation and cytotoxicity of CD4+and CD8+T cells by D1 dopamine receptors:an in vitro analysis[J].Int Immunopharmacol,2001,1(7):1363-1374.
Asada M,Ebihara S,Numachi Y,et al.Reduced tumor growth in a mouse model of schizophrenia,lacking the dopamine transporter[J].Int J Cancer,2008,123(3):511-518.
[13]
Sachlos E,Risueno RM,Laronde S,et al.Identification of drugs including a dopamine receptor antagonist that selectively target cancer stem cells[J].Cell,2012,149(6):1284-1297.
[14]
Dobbeling U,Waeckerle-men Y,Zabel F,et al.The antihistamines clemastine and desLoratadine inhibit STAT3 and c-Myc activities and induce apoptosis in cutaneous T-cell lymphoma cell lines[J].Exp Dermatol,2013,22(2):119-124.
[15]
Hadzijusufovic E,Peter B,Gleixner KV,et al.H1-receptor antagonists terfenadine and Loratadine inhibit spontaneous growth of neoplastic mast cells[J].Exp Hematol,2010,38(10):896-907.
[16]
Soule BP,Simone NL,Degraff WG,et al.Loratadine dysregulates cell cycle progression and enhances the effect of radiation in human tumor cell lines[J].Radiat Oncol,2010,3(5):8.
[17]
Medjber K,Freidja ML,Grelet S,et al.Role of nicotinic acetylcholine receptors in cell proliferation and tumour invasion in broncho-pulmonary carcinomas[J].Lung Cancer,2015,87(3):258-264.
[18]
Park MS,Dong SM,Kim BR,et al.Thioridazine inhibits angiogenesis and tumor growth by targeting the VEGFR-2/ PI3K/mTOR pathway in ovarian cancer xenografts[J].Oncotarget,2014,5(13):4929.
[19]
Spengler G,Csonka A,Molnar J,et al.The anticancer activity of the old Neuroleptic Phenothiazine-type drug Thioridazine[J].Anticancer Res,2016,36(11):5701-5706.
[20]
Chen JS,Lin SY,Tso WL,et al.Checkpoint kinase 1-mediated phosphorylation of Cdc25C and bad proteins are involved in antitumor effects of Loratadine-induced G2/M phase cell-cycle arrest and apoptosis[J].Mol Carcinog,2006,45(7):461-478.