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대장암 세포주의 개별 항암화학요법에 대한 침습성과 약제감수성

Invasiveness of and Drug Sensitivity to Various Anti-cancer Regimens in Five Colorectal Cancer Cell Lines

대한대장항문학회지 2010년 26권 2호 p.98 ~ 104
이유미 ( Lee Yu-Mi ) - 울산대학교 의과대학 외과학교실

윤용식 ( Yoon Yong-Sik ) - 울산대학교 의과대학 외과학교실
김진천 ( Kim Jin-Cheon ) - 울산대학교 의과대학 외과학교실
노선애 ( Roh Seon-Ae ) - 울산대학교 의과대학 외과학교실
조동형 ( Cho Dong-Hyung ) - 울산대학교 의과대학 외과학교실

Abstract


Purpose: Colorectal cancer (CRC) is one of the leading causes of cancer death in South Korea. Angiogenesis has been associated with invasion and metastasis of tumors and with the secretion of various growth factors. Bevacizumab is a humanized monoclonal antibody that recognizes and blocks vascular endothelial growth factor (VEGF) and that targets integrin αVβ3 and matrix metalloproteinases (MMPs) as angiogensis inhibitors. The aims of this study were identification of the mechanism of target molecules related to angiogenesis and demonstration of identifiable invasion by using chemotherapeutic regimens in vitro.

Methods: The five colorectal cancer cell lines were treated with bevacizumab using standard or combined regimens. The expression of integrin αVβ3 was detected and the investigation of apoptosis was done by using flow cytometry. The activations of MMP-2 and MMP-9 were measured by using gelatin zymography.

Results: The apoptotic cell death was significantly increased for the combined regimens, especially for FOLFOX (5-FU, leucovorin, and oxaliplatin) with bevacizumab. Bevacizumab inhibited the expression of integrin αVβ3 in the HT29 (59%), LoVo (67%), and SW480 (17%) cell lines, but did not in the AMC5 and the RKO cell lines. The activations of MMP-2 and MMP-9 were significantly reduced by treatment with bevacizumab in the HT29 and the LoVo cell lines. In the HT29 and the LoVo cell lines, thus, bevacizumab inhibited invasion and metastasis activity through down-regulation of integrin αVβ3 and MMPs.

Conclusion: Our results provide biological evidence of potent angiogenic activity and indicate that angiogenesis is a complex process that involves multiple factors, including VEGF, integrin αVβ3, and MMPs.

키워드

대장암;항암화학요법;베바시쭈멥;신생혈관
Colorectal cancer;Chemotherapy;Bevacizumab;Angiogenesis
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