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CisplatinumÅõ¿©·Î ³»¼º À¯µµµÈ ¹æ±¤¾Ï ¼¼Æ÷ÁÖ¿¡¼­ Ç×¾ÏÁ¦ °¨¼ö¼º ¹× ¼¼Æ÷ÇÐÀû Ư¼ºÀÇ º¯È­ Change of Chemosensitivity and Cellular Characteristics of Cisplatinum Resistant Human Bladder Cancer Cells Induced by Long-term Cisplatinum Treatment

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ÀÌÀº½Ä/Eunsik Lee ¹Î°æÁØ/±è¼ö¿õ/ÀÌÇØ¿ø/Á¶±Ô¼±/±è±¤¸í/ÀÌ»óÀº/ÀÌÁ¾¿í/Kyung Joon Min/Soo Woong Kim/Hae Won Lee/Kyu Seo Cho/Kwang Myung Kim/Sang Eun Lee/Chongwook Lee

Abstract

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¹æ±¤ÀÇ ÀÌÇà»óÇǾÏÀº ºñ´¢±â°ú ¿µ¿ª¿¡¼­ °¡Àå ºóµµ°¡ ³ôÀº ¾Ç¼ºÁ¾¾çÀ̸ç Áø´Ü ´ç½Ã ÁøÇà
¼º ¹æ±¤¾ÏÀÌ ÀüüÀÇ ¾à 30%¸¦ Â÷ÁöÇÑ´Ù. ÁøÇ༺ ¹æ±¤¾Ï¿¡´Â cisplaunumµî plantinum °è¿­
À» Áß½ÉÀ¸·Î ÇÑ º´ÇÕÈ­Çпä¹ýÀÌ ÁÖµÈ Ä¡·á¹ýÀ¸·Î ÀÌ¿ëµÇ°í ÀÖÀ¸³ª ºÎºÐ°üÇØ¿Í ¿ÏÀü°üÇظ¦
ÇÕÇÑ Ä¡·á ¼ºÀûÀÌ 30-50%¿¡ ºÒ°úÇÏ¿© ±â´ë¿¡ ¸ø ¹ÌÄ¡°í ÀÖÀ¸¸ç, ±× ÁÖµÈ ¿øÀÎÀº Ç×¾ÏÁ¦¿¡
´ëÇÏ¿© ³»¼ºÀ» °®´Â ¾Ï¼¼Æ÷ÀÇ ¹ßÇöÀÌ ¶ó°í »ý°¢µÈ´Ù.
¿©·¯ °¡Áö Á¾·ùÀÇ ¾Ï¼¼Æ÷ÁÖ¿¡¼­ cisplatinum¿¡ ³»¼ºÀ» º¸ÀÌ´Â ³»¼º ¼¼Æ÷ÁÖ°¡ ¼ö¸³µÇ¾ú°í
À̸¦ ÀÌ¿ëÇÑ ±â¿ÕÀÇ ¿¬±¸¿¡¼­ cisplatinum¿¡ ´ëÇÑ ¾Ï¼¼Æ÷ÀÇ ³»¼º ±âÀüÀ¸·Î´Â ¼¼Æ÷³»
cisplatinumÃàÀûÀÇ °¨¼Ò, glutathione°ú ±× °ü·ÃÈ¿¼Ò¿¡ ÀÇÇÑ ¾àÁ¦ÀÇ Çص¶ DNA repair°úÁ¤ÀÇ
Ç×Áø µîÀÌ ¹àÇôÁ³À¸¸ç glutathione°ú ±× °ü·ÃÈ¿¼ÒÀÇ ´ë»ç°¡ ÁÖµÈ ³»¼º ±âÀüÀ¸·Î ¾Ë·ÁÁö°í
ÀÖ´Ù ±×·¯³ª ¹æ±¤¾ÏÀÇ °æ¿ì¿¡´Â ¼ö¸³µÈ cisplatinum³»¼º ¼¼Æ÷ÁÖÀÇ ¼ö°¡ ÀûÀ» »Ó ¾Æ´Ï¶ó ±×
³»¼º ±âÀü¿¡ ´ëÇÑ º¸°íµµ ¸¹Áö ¾Ê´Ù.
ÀúÀÚµéÀº Àú³óµµÀÇ cisplatlnum¿¡ Àå±â°£ ³ëÃâ½ÃÄÑ ¼ö¸³µÈ ³»¼º ¼¼Æ÷ÁÖ¿¡¼­ cisplatinum¿¡
´ëÇÑ °¨¼ö¼ºÀº º¯È­ÇÏ¿´Áö¸¸ mdrÀ¯ÀüÀÚÀÇ ¹ßÇö°ú glutathione ÇÔ·®ÀÌ º¯È­°¡ ¾øÀ½À» º¸°íÇÑ
¹Ù ÀÖ´Ù. º» ¿¬±¸¿¡¼­´Â Àú³óµµÀÇ cisplatinum¿¡ Àå±â°£ ³ëÃâ½ÃÄÑ ¼ö¸³ÇÑ ³»¼º ¼¼Æ÷ÁÖ¸¦ °í
³óµµÀÇ cisplatinum¿¡ Àå±â°£ ³ëÃâ½ÃÄ×À» °æ¿ì Ç×¾ÏÁ¦ °¨¼ö¼º ¹× ¼¼Æ÷ÇüÅÂ, ¼¼Æ÷¼ºÀå, DNA
ÇÕ¼º´É, ¼¼Æ÷Áֱ⠵îÀÇ ¼¼Æ÷ Ư¼ºÀÇ º¯È­¸¦ °üÂûÇÏ¿´´Ù
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Purpose : Cisplatinum has the therapeutic efficacy against a bladder cancer. However,
the response is often limited due to appearance of drug-resistant tumor cells. The
studies of establishment and characterization of cisplatinum-resistant tumor cells are
considered to be helpful in elucidating the underlying mechanism of acquired resistance
to cisplatinum in human tumors.
Materials and Methods : We established cisplatinum-resistant cell lines sequentially,
T24Rl and T24R2, which show resistance to cisplatinum at a concentration of 1 and 2§¶
/ml, respectively, by the stepwise exposure of T24 human bladder cancer cell to
increasing concentrations of cisplatinum.
Results : The resistance to cisplatinum of T24Rl and T24R2 cells was 13- and
18-fold that of the parental T24 cells, respective1y. Growth, DNA synthesis and cell
cycle distribution of T24Rl and T24R2 cells were not different from those of the
parental T24 cells.
Conclusions : These cisplatinum-resistant bladder tumor cell lines could be a useful
model to elucidate the biochemical and molecular mechanism Involved In the cisplatinum
resistance.

Å°¿öµå

Bladder neoplasms; Cell line; Cisplatinum; Drug-resistance;

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