Evaluation of antitumor activity of a TGF-beta receptor I inhibitor (SD-208) on human colon adenocarcinoma

被引：25

作者：

Akbari, Abolfazl ^{[1
]}

Amanpour, Saeid ^{[2
]}

Muhammadnejad, Samad ^{[2
]}

Ghahremani, Mohammad Hossein ^{[1
,3
]}

Ghaffari, Seyed Hamidollah ^{[4
]}

Dehpour, Ahmad Reza ^{[5
]}

Mobini, Gholam Reza ^{[1
]}

Shidfar, Fatemeh ^{[1
]}

Abastabar, Mahdi ^{[6
]}

Khoshzaban, Ahad ^{[7
]}

Faghihloo, Ebrahim ^{[9
]}

Karimi, Abbas ^{[10
]}

Heidari, Mansour ^{[7
,8
]}

机构：

[1] Univ Tehran Med Sci, Sch Adv Med Technol, Dept Mol Med, Tehran, Iran

[2] Univ Tehran Med Sci, Canc Res Ctr, Canc Inst Iran, Tehran, Iran

[3] Univ Tehran Med Sci, Fac Pharm, Dept Pharmacol & Toxicol, Tehran, Iran

[4] Univ Tehran Med Sci, Shariati Hosp, Hematol Oncol & Stem Cell Transplantat Res Ctr, Tehran, Iran

[5] Univ Tehran Med Sci, Sch Med, Dept Pharmacol, Tehran, Iran

[6] Mazandaran Univ Med Sci, Sch Med, Dept Med Mycol & Parasitol, Invas Fungi Res Ctr, Sari, Iran

[7] Univ Tehran Med Sci, Farabi Eye Hosp, Stem Cells Preparat Uinte, Tehran, Iran

[8] Univ Tehran Med Sci, Sch Med, Dept Med Genet, Tehran, Iran

[9] Univ Tehran Med Sci, Sch Publ Hlth, Dept Virol, Tehran, Iran

[10] Iran Univ Med Sci, Fac Adv Technol Med FATiM, Dept Mol Med, Tehran, Iran

来源：

DARU-JOURNAL OF PHARMACEUTICAL SCIENCES | 2014年 / 22卷

关键词：

SD-208; Colorectal cancer; SW-48; Immunohistochemistry staining; KINASE INHIBITOR; GROWTH; CANCER; VIVO; CARCINOMA; MURINE;

D O I：

10.1186/2008-2231-22-47

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Background: Transforming growth factor-beta (TGF-beta) pathway is involved in primary tumor progression and in promoting metastasis in a considerable proportion of human cancers such as colorectal cancer (CRC). Therefore, blockage of TGF-beta pathway signaling via an inhibitor could be a valuable tool in CRC treatment. Methods: To evaluate the efficacy of systemic targeting of the TGF-beta pathway for therapeutic effects on CRC, we investigated the effects of a TG beta RI (TGF-beta receptor 1) or T beta RI kinase inhibitor, SD-208, on SW-48, colon adenocarcinoma cells. In this work, in vitro cell proliferation was studied by methyl thiazolyl tetrazolium (MTT) and bromo-2'-deoxyuridine (BrdU) assays. Also, the histopathological and immunohistochemical evaluations were conducted by hematoxylin and eosin, and Ki-67 and CD34 markers were stained, respectively. Results: Our results showed no significant reduction in cell proliferation and vessel formation (170 +/- 70 and 165 +/- 70, P > 0.05) in treated SW-48 cells with SD-208 compared to controls. Conclusion: Our data suggested that SD-208 could not significantly reduce tumor growth and angiogenesis in human colorectal cancer model at least using SW-48 cells.

引用

页数：7

共 23 条

[1] TGF-β and cancer [J].

Bierie, B ;

Moses, HL .

CYTOKINE & GROWTH FACTOR REVIEWS, 2006, 17 (1-2) :29-40

[2] TGFβ:: the molecular Jekyll and Hyde of cancer [J].

Bierie, Brian ;

Moses, Harold L. .

NATURE REVIEWS CANCER, 2006, 6 (07) :506-520

[3]

Bruna A, 2003, CANCER RES, V63, P7791

[4] Inhibition of growth and metastasis of mouse mammary carcinoma by selective inhibitor of transforming growth factor-β type I receptor kinase in vivo [J].

Ge, Rongrong ;

Rajeev, Vaishali ;

Ray, Partha ;

Lattime, Edmund ;

Rittling, Susan ;

Medicherla, Satya ;

Protter, Andy ;

Murphy, Alison ;

Chakravarty, Jit ;

Dugar, Sundeep ;

Schreiner, George ;

Barnard, Nicola ;

Reiss, Michael .

CLINICAL CANCER RESEARCH, 2006, 12 (14) :4315-4330

[5] Selective evolution of stromal mesenchyme with p53 loss in response to epithelial tumorigenesis [J].

Hill, R ;

Song, YR ;

Cardiff, RD ;

Van Dyke, T .

CELL, 2005, 123 (06) :1001-1011

[6] SB-431542 is a potent and specific inhibitor of transforming growth factor-β superfamily type I activin receptor-like kinase (ALK) receptors ALK4, ALK5, and ALK7 [J].

Inman, GJ ;

Nicolás, FJ ;

Callahan, JF ;

Harling, JD ;

Gaster, LM ;

Reith, AD ;

Laping, NJ ;

Hill, CS .

MOLECULAR PHARMACOLOGY, 2002, 62 (01) :65-74

[7]

Jean-Jacques L, 2012, ISRN MOL BIOL, V7, P1

[8] Cancer statistics, 2008 [J].

Jemal, Ahmedin ;

Siegel, Rebecca ;

Ward, Elizabeth ;

Hao, Yongping ;

Xu, Jiaquan ;

Murray, Taylor ;

Thun, Michael J. .

CA-A CANCER JOURNAL FOR CLINICIANS, 2008, 58 (02) :71-96

[9]

Khalid SM, 2011, CANCER RES, V71, P175

[10]

Kinzler K.W., 2002, The genetic basis of human cancer, P583

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