Down‐regulation of c‐Myc expression inhibits the invasion of bile duct carcinoma cells

Cholangiocarcinoma is the second most common primary hepatic tumour originating from biliary tract epithelial cells with poor prognosis. Enhanced c‐Myc protein expression contributes to many aspects of tumour cell biology. Although the ability of c‐Myc to drive unrestricted cell proliferation and to inhibit cell differentiation had been well recognized, whether down‐regulated c‐Myc expression can inhibit tumour cell invasion still remains to be explored. The c‐Myc ASODN (antisense oligodeoxyribonucleotide) and NSODN (nonsense oligodeoxyribonucleotide) were designed, synthesized and transfected into human QBC939 bile duct carcinoma cells using the Lipofectamine 2000 reagent. The protein expression of c‐Myc was detected by Western blot. A transwell experiment was applied to evaluate the invasive capacity of the QBC939 cells. c‐Myc ASODN could significantly suppress the c‐Myc protein expression (P<0.05) and the invasion (P<0.01) of QBC939 cells transfected with c‐Myc ASODN compared with that in the control and c‐Myc NSODN‐transfected group. Thus in the present study we show that down‐regulation of c‐Myc expression can inhibit the invasion of QBC939 cells in vitro.

[1]  B. Aggarwal,et al.  Curcumin decreases cholangiocarcinogenesis in hamsters by suppressing inflammation‐mediated molecular events related to multistep carcinogenesis , 2011, International journal of cancer.

[2]  M. Henriksson,et al.  MYC in oncogenesis and as a target for cancer therapies. , 2010, Advances in cancer research.

[3]  W. Gu,et al.  Non-transcriptional control of DNA replication by c-Myc , 2007, Nature.

[4]  K. Arihiro,et al.  Immunohistochemical and mutational analyses of Wnt signaling components and target genes in intrahepatic cholangiocarcinomas. , 2005, International journal of oncology.

[5]  Alphonse E. Sirica,et al.  Cholangiocarcinoma: Molecular targeting strategies for chemoprevention and therapy , 2005, Hepatology.

[6]  J. Plevris Risk factors of intrahepatic cholangiocarcinoma in the United States : a case-control study , 2005 .

[7]  Yun Huang,et al.  Diagnostic and surgical therapeutic features of extrahepatic bile duct carcinoma without jaundice. , 2004, World journal of gastroenterology.

[8]  Yan-Hong Gu,et al.  Coordinate increase of telomerase activity and c-Myc expression in Helicobacter pylori-associated gastric diseases. , 2004, World journal of gastroenterology.

[9]  M. Olnes,et al.  A Review and Update on Cholangiocarcinoma , 2004, Oncology.

[10]  H. El‐Serag,et al.  The epidemiology of cholangiocarcinoma. , 2004, Seminars in liver disease.

[11]  A. Xu,et al.  Function of apoptosis and expression of the proteins Bcl-2, p53 and C-myc in the development of gastric cancer. , 2001, World journal of gastroenterology.

[12]  H. Thomas,et al.  Increase in mortality rates from intrahepatic cholangiocarcinoma in England and Wales 1968–1998 , 2001, Gut.

[13]  Y. Kawakubo,et al.  Interrelationship between Epstein–Barr virus infection in gastric carcinomas and the expression of apoptosis‐associated proteins , 2001, Histopathology.

[14]  M. S. Lee,et al.  c-Myc expression is related with cell proliferation and associated with poor clinical outcome in human gastric cancer. , 1999, Journal of Korean medical science.

[15]  S. R. Young,et al.  c-myc and chromosome 8 centromere studies of ovarian cancer by interphase FISH. , 1999, Experimental and molecular pathology.

[16]  Chi V. Dang,et al.  c-Myc Target Genes Involved in Cell Growth, Apoptosis, and Metabolism , 1999, Molecular and Cellular Biology.

[17]  S. Kimura,et al.  Alterations of c-myc expression by antisense oligodeoxynucleotides enhance the induction of apoptosis in HL-60 cells. , 1995, Cancer research.

[18]  R. Lidereau,et al.  Genetic alteration of the c-myc protooncogene (MYC) in human primary breast carcinomas. , 1986, Proceedings of the National Academy of Sciences of the United States of America.

[19]  J. Minna,et al.  Amplification and expression of the c-myc oncogene in human lung cancer cell lines , 1983, Nature.