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자궁내막암 세포주 Hec-1A에서 sorafenib과 celecoxib에 의한 세포증식억제와 혈관내피 성장인자의 발현 변화

Synergistic effects of sorafenib and celecoxib inhibit growth and VEGF expression in Hec-1A endometrial cancer cell line

배동한|남계현|박보라|김정식
대한산부인과학회 (Korean Soceity of Obstetrics and Gynecology)|2012.11|Obstetrics & Gynecology Science|제55권 제11호|pp. 814-821|DOI http://dx.doi.org/10.5468/KJOG.2012.55.11.814

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SorafenibVascular endothelial growth factorEndometrial cancerCelecoxib혈관내피성장인자자궁내막암 세포주
주제분류산부인과학

초록

목적자궁내막암 세포주 Hec-1A에서 sorafenib과 celecoxib에 의한 세포증식억제 및 혈관내피성장인자(vascular endothelial growth factor,VEGF)의 발현 변화에 대해 연구하고자 하였다. 연구방법Hec-1A 세포주에 대한 sorafenib과 celecoxib의 처치 농도와 시간에 따른 세포증식억제 작용을 (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay로 측정하였으며, 또한 위 약제들을 단독 또는 병합투여 시VEGF, p53의 변화를 역전사-중합효소연쇄반응(reverse transcription-polymerase chain reaction)으로 측정하였다. 결과Sorafenib과 celecoxib 각각을 자궁내막암 세포주인 Hec-1A에 처치 시, sorafenib의 농도를 5 ng/mL, 10 ng/mL, 20 ng/mL, 50 ng/mL로증가시킬수록 모든 농도에서 의미 있게 점차적으로 세포들의 증식이 억제되었으며, celecoxib는 60 μmol/L의 농도에서부터 통계적으로유의하게 차이가 났다. Sorafenib 10 ng/mL을 단독 처리하였을 때보다 celecoxib를 병합처리하였을 때 약제 간 상승 작용으로 세포증식억제의 차이가 통계적으로 의미 있게 나타났다(P ＜0.0001). 혈관신생과 관련된 VEGF는 sorafenib과 celecoxib 두 가지 약제를 동시에 병합시 sorafenib 단독 처치보다 발현감소가 의미 있게 나타났다. 그러나 p53의 경우 sorafenib이나 celecoxib를 각각 또는 병합처리하며 시간과 농도를 다르게 하여도 약제들에 따른 발현의 변화는 나타나지 않았다. 결론본 연구결과로 sorafenib과 celecoxib의 병합처치에 의해 Hec-1A자궁내막암 세포주의 증식과 VEGF의 발현이 억제되므로, 자궁내막암의기존 치료요법에 위 약제들이 보조적인 역할을 할 수 있으리라 생각된다.

Abstract

Objective The aim of this study was to investigate whether combination of sorafenib and celecoxib exhibited an anti-tumor effi cacy or altered expression of vascular endothelial growth factor (VEGF) in Hec-1A endometrial cancer cell line. Methods To determine whether sorafenib or celecoxib-induced growth inhibition was determined by the (3-[4,5-dimethylthiazol-2-yl]-5-[3-carboxymethoxyphenyl]-2-[4-sulfophenyl]-2H-tetrazolium, inner salt) assay. Expression of VEGF and p53 were evaluated using the reverse transcription polymerase chain reaction. Results Combination of sorafenib 10 ng/mL and celecoxib 50 μmol/L exhibited synergistic inhibitory effects compared to treatment with each agent alone (P <0.0001). VEGF expression was also down regulated after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib in Hec-1A cells. However, there was no alteration of p53 expression in Hec-1A cells after 24 hours or 72 hours of treatment with sorafenib alone or in combination with sorafenib and celecoxib. Conclusion Combination treatment of sorafenib and celecoxib to Hec-1A endometrial cancer cell line revealed the ability to inhibit growth and expression of VEGF.

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