Carcinogenesis Advance Access published online on December 19, 2005
Carcinogenesis, doi:10.1093/carcin/bgi316
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1 Institute of Pharmacology, College of Medicine, National Yang-Ming University, Shih-Pai, Taipei 11221, Taiwan, ROC
* To whom correspondence should be addressed. The present work was conducted to further examine the effects of thymosin
Received November 18, 2005
Revised December 11, 2005
Accepted December 13, 2005
CANCER BIOLOGY
Overexpression of thymosin
Hung-Liang Hsiao 1,
Wei-Shu Wang 2,
Po-Min Chen 2,
and
Yeu Su 3 *
-4 renders SW480 colon carcinoma cells more resistant to apoptosis triggered by FasL and two topoisomerase II inhibitors via down-regulating Fas and up-regulating Survivin expression, respectively
2 Division of Medical Oncology, Department of Medicine, Taipei Veterans General Hospital, Taipei, Taiwan, ROC
3 Institute of Biopharmaceutical Science, Collage of Life Science, National Yang-Ming University, Taipei, Taiwan, ROC
Yeu Su, E-mail: yeusu{at}ym.edu.tw
Abstract 
-4 (T4) upregulation on the apoptosis of SW480 colon cancer cells induced by T-cells and various chemotherapeutic agents because reduced susceptibility to the cytotoxicity of an anti-Fas IgM (CH-11) in T4-overexpressing cells has previously been reported by us. As expected, T4 overexpressers were also more resistant to the killing effect of FasL-bearing Jurkat T cells. On the other hand, pretreating these cells with an MMP inhibitor restored not only their Fas levels but also their sensitivity to CH-11, suggesting a pivotal role of MMP in downregulating Fas in T4 overexpressers. Interestingly, while the susceptibilities of T4 overexpressers to 5-FU and irinotecan remained unchanged, they were more resistant to doxorubicin and etoposide which triggered apoptosis via a mitochondrial pathway. Concordantly, activation of both caspase-9 and caspase-3 in T4 overexpressers by the two aforementioned topoisomerase II inhibitors was dramatically abrogated which could be accounted mainly by an increased expression of Survivin, a critical anti-apoptotic factor. Finally, poor survival was found in stage III colon cancer patients whose tumors were stained positively by the anti-Survivin antibody. Thus, advantages such as immune evasion and resistance to anticancer drug-induced apoptosis acquired by colon cancer cells through T4 overexpression might facilitate their survival during metastasis and chemotherapy.-4; colon cancer; Fas; MMP-7; drug resistance; Survivin.
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