rTSbeta as a novel 5-fluorouracil resistance marker of colorectal cancer: a preliminary study.
BACKGROUND
Colorectal cancer is the most common form of malignancy in Taiwan and the third leading cause of death from cancer, preceded only by lung and hepatic cancers. Colorectal cancer is typically treated by surgical intervention and/or chemotherapy and radiotherapy, if necessary. To date, 5-fluorouracil (5-FU) is the most commonly used anti-cancer chemotherapy drug. However, patients commonly experience resistance to the drug therefore limiting its efficiency. In this study, we measured the expression of rTSbeta in human colon cancer as a novel 5-FU resistance marker.


METHODS
We collected 172 colon cancer samples from 4 different hospitals (including 21 pairs of colon cancer biopsies and 151 pathologic slides of colon cancer). In vitro, we measured the cytotoxicity of 5-FU and 5-FU plus leucovorin in H630 and H630-1 colon cancer cell lines.


RESULTS
The results revealed that rTSbeta was expressed in 115 (66.9 %) pathology samples and that tumour expression was higher than in corresponding normal tissue. Survival rates of up to 5 years following treatment was significantly higher for patients without rTSbeta expression than for those with rTSbeta expression (P = 0.0023). In vitro, H630-1 (with rTSbeta overexpression) had significantly higher IC50 of 5-FU than did H630. IC50 of 5-FU decreased when leucovorin was added.


CONCLUSIONS
Results indicate a close relationship between rTSbeta expression and resistance to the drug 5-FU in human colorectal cancer. These results provide further evidence for rTSbeta expression as a novel 5-FU resistance marker of colorectal cancer.
Lin
Yu-Li
YL
Division of Pediatric Surgery, Department of Surgery, Cheng Ching Hospital, Taiwan, ROC.
Chow
Kuan-Chih
KC
D015415:Biomarkers; D045744:Cell Line, Tumor / Q000187:drug effects; D015179:Colorectal Neoplasms / Q000188:drug therapy*; D003584:Cytological Techniques; D019008:Drug Resistance, Neoplasm / Q000502:physiology*; D005472:Fluorouracil / Q000494:pharmacology* / Q000627:therapeutic use*; D006801:Humans; D066298:In Vitro Techniques; D013624:Taiwan; D013940:Thymidylate Synthase / Q000235:genetics / Q000378:metabolism*
D015415:Biomarkers; D013940:Thymidylate Synthase; D005472:Fluorouracil