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Change in Expression of Survivin Caused by Using Oxaliplatin in HCT116 Colon Cancer Cells

대한대장항문학회지 2010년 26권 4호 p.246 ~ 253
손원준 ( Son Won-Jun ) - 단국대학교 의과대학 외과학교실

이정원 ( Lee Jung-Won ) - 단국대학교 의과대학 외과학교실
박동국 ( Park Dong-Guk ) - 단국대학교 의과대학 외과학교실

Abstract


Purpose: Oxaliplatin is a third-generation platinum compound, and it has no nephrotoxicity and has reduced bone marrow toxicity. Cancer cells that are resistant to cisplatin are sensitive to oxaliplatin. Oxaliplatin is used widely for the treatment of colon cancers. Recently, oxaliplatin was reported to inhibit the expression of survivin, which protects cell apoptosis. However, there are no reports on the expressions of survivin variants and the changes in intracellular localization of survivin in cancer cells. We studied the expression of survivin caused by oxaliplatin in HCT116 colon cancer cells, and we observed the localization of survivin in the mitotic phase.

Methods: We treated the HCT116 colon cancer cells with 2.0 μM of oxaliplatin, and we studied the expressions of survivin protein, and survivin mRNA variants, as well as the changes in intracellular localization, by using the Western blot method, RT-PCR, immunocytochemistry, and flowcytometry.

Results: Oxaliplatin inhibits the expression of the survivin protein and survivin mRNA in HCT116 colon cancer cells. The expression of the survivin-2B variants, which have no antiapoptotic activity but control cell mitosis by localization on a microtubule, is reduced continuously 2 days after treatment with oxaliplatin. In immunocytochemistry, expression of survivin in the cytoplasm is reduced and especially is not expressed in microtubules and contractile rings.

Conclusion: One of the mechanisms of oxaliplatin is to inhibit the expression of and to change the localization of survivin. Based on these results, we suggest that changes in the expression of survivin variants and in their localization are two effects of oxaliplatin.

키워드

Oxaliplatin; Survivin; Colorectal cancer; Mitosis; Microtubule
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