title: Tamoxifen can reverse multidrug resistance of colorectal carcinoma in vivo.
abstract: OBJECTIVE
  To investigate the effect of tamoxifen (TAM) on multidrug resistance (MDR) of colorectal carcinoma in vivo and its relationship with estrogen receptor (ER).
  
  
  METHODS
  Multidrug resistance was determined by means of semi-quantitative retro-transcription polymerase chain reaction (RT-PCR) to test mdr1 gene mRNA and ER expression was studied by immunohistochemistry. Tumor tissues from three cases of human colon carcinoma, which had mdr1(+)/ER(+), mdr1(+)/ER(-), mdr1(-) expressions, were planted subcutaneously in the neck of nude mice to establish three xenograft models. These models were subdivided into four subgroups randomly: Doxorubicin (DOX)-treated group, TAM-treated group, DOX and TAM group and control group. The dimensions of these xenografts were measured after each course of treatment and the xenografts were removed at the end of the experiments for measurements of weight and the variation of mdr1 mRNA level with RT-PCR. In each course, TAM (15 mg/(kg/d)) was administrated orally per day in the first seven days and DOX (3.6 mg/kg) was injected peritoneally on the first day. Data was evaluated by q and t tests.
  
  
  RESULTS
  In the animal models with mdr1(-) tumor, the weights and volumes of the planted tumor in DOX group ((39.1+/-2.29) mg, (31.44+/-1.61) mm(3)) and TAM and DOX group ((38.72+/-2.56) mg, (31.31+/-1.74) mm(3)), which were lesser than that of control group ((45.48+/-3.92) mg, (36.42+/-2.77)mm(3), P = 0.037, P = 0.016 respectively) significantly. In the animal models with mdr1(+)/ER(+) tumor, the weights and volumes of planted tumor were not affected by DOX or TAM treatment; however, in TAM and DOX group ((425.5+/-28.58) mg, (340.35+/-22.28) mm(3)), they were significantly less than that of control group ((634.23+/-119.41) mg, (507.45+/-93.34) mm(3), P = 0.022, P = 0.045 respectively), which are similar to that in the models with mdr1(+)/ER(-) tumor. No significant changes were found in the expressive level of mdr1 mRNA following these treatments.
  
  
  CONCLUSIONS
  The expression of mdr1 gene corresponds to the sensitivity of colon cancer to anti-tumor drugs in vivo. TAM can reverse the MDR of colorectal carcinoma in nude mice, which is independent of the expression of ER; however, no change was observed in the expressive level of mdr1 mRNA.
authors.affiliation: Department of Gastroenterology, First Affiliated Hospital, Nanjing Medical University, Nanjing 210029, Jiangsu Province, China. shen_li_zong@yahoo.com
authors.forename: Li-Zong
authors.initials: LZ
authors.lastname: Shen
authors.forename: Yi-Bing
authors.initials: YB
authors.lastname: Hua
authors.forename: Xue-Ming
authors.initials: XM
authors.lastname: Yu
authors.forename: Qing
authors.initials: Q
authors.lastname: Xu
authors.forename: Tao
authors.initials: T
authors.lastname: Chen
authors.forename: Jian-Hua
authors.initials: JH
authors.lastname: Wang
authors.forename: Wen-Xi
authors.initials: WX
authors.lastname: Wu
mesh_terms: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics; D000818:Animals; D018931:Antineoplastic Agents, Hormonal / Q000494:pharmacology*; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000473:pathology / Q000503:physiopathology; D018432:Drug Resistance, Multiple / Q000187:drug effects* / Q000235:genetics; D019008:Drug Resistance, Neoplasm / Q000187:drug effects / Q000235:genetics; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D012333:RNA, Messenger / Q000032:analysis; D011960:Receptors, Estrogen / Q000235:genetics; D013629:Tamoxifen / Q000494:pharmacology*; D023041:Xenograft Model Antitumor Assays
chemical_list: D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1; D018931:Antineoplastic Agents, Hormonal; D012333:RNA, Messenger; D011960:Receptors, Estrogen; D013629:Tamoxifen
references.citation: Int J Cancer. 2001 Apr 1;92(1):115-22
references.pmid: 11279614
references.citation: J Nucl Med. 2001 Apr;42(4):646-54
references.pmid: 11337555
references.citation: Exp Cell Res. 2000 Apr 10;256(1):300-7
references.pmid: 10739677
references.citation: Eur J Cancer. 2003 Jun;39(9):1251-8
references.pmid: 12763213
references.citation: Anticancer Res. 2004 Mar-Apr;24(2B):859-64
references.pmid: 15161038
references.citation: Cancer Lett. 2000 Dec 8;161(1):63-71
references.pmid: 11078914
references.citation: Hum Pathol. 2001 Sep;32(9):940-4
references.pmid: 11567223
references.citation: Am J Clin Pathol. 2000 Mar;113(3):364-8
references.pmid: 10705816
references.citation: Nucl Med Biol. 2000 Feb;27(2):135-41
references.pmid: 10773542
references.citation: Int J Oncol. 2002 Nov;21(5):1021-6
references.pmid: 12370750
references.citation: Anticancer Res. 2004 Mar-Apr;24(2A):409-15
references.pmid: 15152938
references.citation: Biochem Biophys Res Commun. 2000 Apr 13;270(2):425-31
references.pmid: 10753641
references.citation: Anticancer Res. 2003 May-Jun;23(3B):2419-24
references.pmid: 12894523
references.citation: Curr Drug Targets Immune Endocr Metabol Disord. 2001 May;1(1):1-12
references.pmid: 12476778
references.citation: Hepatobiliary Pancreat Dis Int. 2004 May;3(2):296-9
references.pmid: 15138130
references.citation: Anticancer Res. 2004 Mar-Apr;24(2B):865-71
references.pmid: 15161039
references.citation: Cancer. 2001 Sep 15;92(6):1556-66
references.pmid: 11745235
references.citation: Int J Cancer. 2000 Sep 1;87(5):615-28
references.pmid: 10925353
references.citation: World J Gastroenterol. 2003 Jul;9(7):1444-9
references.pmid: 12854138
references.citation: Cancer Res. 2001 Jan 15;61(2):632-40
references.pmid: 11212261
references.citation: Anticancer Res. 2003 May-Jun;23(3B):2681-90
references.pmid: 12894558
references.citation: Cancer Res. 2000 Jan 15;60(2):245-8
references.pmid: 10667568
references.citation: Biochem Biophys Res Commun. 2001 Aug 17;286(2):406-13
references.pmid: 11500053
references.citation: Climacteric. 2002 Mar;5(1):3-14
references.pmid: 11974557
references.citation: Anticancer Drugs. 2001 Oct;12(9):769-79
references.pmid: 11593059