사이클로스포린 A 투여 시 불멸화구강각화세포와 구강 편평세포암종 세포주에서 docetaxel 유도 아팝토시스 항진효과
Cyclosporin A Enhance Docetaxel Induced Apoptosis in Immortalized Human Oral Keratinocyte and Human Oral Squamous Cell Carcinoma Cell Line
송영성, 박경주, 이종헌,
소속 상세정보
송영성 ( ) - 단국대학교 치과대학 구강병리학교실
박경주 ( Park Gyeong-Ju ) - 단국대학교 치과대학 구강병리학교실
이종헌 ( Lee Chong-Heon ) - 단국대학교 치과대학 구강병리학교실
KMID : 0829220100340020065
Abstract
Oral squamous cell carcinoma (SCC) is one of the leading causes of cancer mortality worldwide. It is generally thought that adjuvant chemotherapy provides modest prolongation of survival in various carcinoma. Docetaxel (Taxotere, TXT) play a significant role in the treatment of various solid tumors of epithelial origin. CsA (immunosuppressive drug) was widely used as adjunct for the treatment of cancer. Thus, it is important to pursue the apoptosis of IHOK and oral SCC induced by TXT combined with CsA related to the pathogenesis of oral SCC. But TXT combined CsA effect on IHOK and oral SCC remains unclear. After cultured IHOK and HN 22 oral squamous cell carcinoma cell line treated by 10 nM TXT and 1 μM, and caspase inhobitor, respectively, apoptosis index, cytochrome c and caspase-3 -8, -9 mRNA expression by RT-PCR, and procaspase-3 protein amount by immunoslot blotting was prepared. The purpose of this study were to examine the TXT-induced apoptosis pathway via caspase activation by CsA enhancement, and to apply these results to an effective therapeutic treatment plan for oral SCC by TXT combined CsA . 10 nM TXT showed about 60%, 55% celluar apoptosis of IHOK and HN 22, cell line, respectively, while CsA alone did not induce apoptosis in IHOK and HN 22 cell line. 1 μM CsA combined with 10 nM TXT increased apoptosis in IHOK and HN 22 cell line through caspase-3 and cytochrome c mRNA expression, while could not effect on caspase-8 and -9. Caspase inhibitor suppressed apoptosis of IHOK and HN 22 cell line induced by a combination of 1 μM CsA and 10 nM TXT. Immnoslot blotting showed procaspase-3 activation by a combination 1 μM CsA and 10 nM TXT, while caspase inhibitor inhibited activation. It suggested that a combination of CsA and TXT might induce increased apoptosis of IHOK and HN 22 oral squamous cell carcinoma cell line through caspase-3 activation. This treatment with a combination of TXT and CsA may be an effective therapeutic strategy for oral squamous cell carcinoma.
키워드
Apoptosis; Cyclosporin A; Docetaxel; Human Oral SCC Cell Line; IHOK
원문 및 링크아웃 정보
등재저널 정보