title: Down-regulation of BAX gene during carcinogenesis and acquisition of resistance to 5-FU in colorectal cancer.
abstract: Carcinogenesis and resistance to chemotherapy could be as results of expression variations in apoptosis regulating genes. Changes in the expression of apoptosis interfering genes may contribute to colorectal carcinogenesis and resistance to 5-Flourouracil (5-FU) during treatment schedule period. The present study aimed to evaluate the expression of pro-apoptotic and anti-apoptotic genes in colorectal cancer tumor tissues, normal adjacent tissues, and tumor colorectal cancer cell line during acquiring resistance to 5-FU in HT-29 based on Bolus treatment protocol. The normal and tumor tissues were obtained from hospital after surgery and total RNA was extracted for expression analysis. The HT-29 colorectal cancer cell line was cultured and exposed with 5-FU in three stages based on Bolus protocol. The MTT assay and Real Time PCR were carried out to determine the sensitivity to the drug and expression of desired genes, respectively. The obtained data showed that Proapoptotic genes, BAX and BID, were down-regulated in resistant derivate cells compared to wild type HT-29 cells. On the other hand Antiapoptotic genes, CIAP1 and XIAP, showed upregulation in resistant cells compared to wild type ones. Furthermore, BAX and FAS genes showed down-regulation in tumor samples in comparison to normal adjacent tissues. In conclusion, the results of our study suggest that BAX down-regulation could contribute as an important factor during both colorectal carcinogenesis and cell resistance to 5-FU.
authors.affiliation: Cellular and Molecular Biology Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.
authors.forename: Mehdi
authors.initials: M
authors.lastname: Manoochehri
authors.forename: Ashraf
authors.initials: A
authors.lastname: Karbasi
authors.forename: Mojgan
authors.initials: M
authors.lastname: Bandehpour
authors.forename: Bahram
authors.initials: B
authors.lastname: Kazemi
mesh_terms: D017209:Apoptosis / Q000187:drug effects / Q000235:genetics; D051023:BH3 Interacting Domain Death Agonist Protein / Q000235:genetics; D063646:Carcinogenesis / Q000235:genetics*; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000188:drug therapy* / Q000235:genetics*; D015536:Down-Regulation / Q000187:drug effects / Q000235:genetics*; D019008:Drug Resistance, Neoplasm / Q000235:genetics*; D005260:Female; D005472:Fluorouracil / Q000627:therapeutic use*; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D019073:HT29 Cells; D006801:Humans; D051034:Inhibitor of Apoptosis Proteins / Q000235:genetics; D008297:Male; D008875:Middle Aged; D051636:X-Linked Inhibitor of Apoptosis Protein / Q000235:genetics; D051028:bcl-2-Associated X Protein / Q000235:genetics*; D019014:fas Receptor / Q000235:genetics
chemical_list: C494826:BAX protein, human; D051023:BH3 Interacting Domain Death Agonist Protein; C494814:BID protein, human; D051034:Inhibitor of Apoptosis Proteins; D051636:X-Linked Inhibitor of Apoptosis Protein; C496866:XIAP protein, human; D051028:bcl-2-Associated X Protein; D019014:fas Receptor; D005472:Fluorouracil