Hydroxycamptothecin induces apoptosis and inhibits tumor growth in colon cancer by the downregulation of survivin and XIAP expression

World Journal of Surgical Oncology

Yuan Weng¹  Alfred L Chi³  Bojian Fei² 

[1] Department of Thoracic and Cardiovascular Surgery, No.4 people’s Hospital, Wuxi City, 214062, PR China;Department of Surgical Oncology, No.4 people’s hospital, Wuxi City, 214062, PR China;CHI Scientific, Inc., 63 Great Road, Maynard, MA, 01754, USA

关键词: Chemotherapy;    Colon cancer;    5-fluorouracil;    10-Hydroxycamptothecin;   

Others  :  823944
DOI  :  10.1186/1477-7819-11-120

 received in 2012-11-15, accepted in 2013-05-12,  发布年份 2013

【 摘 要 】

Background

10-Hydroxycamptothecin (10-HCPT), isolated from a Chinese tree Camptotheca acuminate, inhibits the activity of topoisomerase I and has a broad spectrum of anticancer activity in vitro and in vivo. It has been shown that HCPT is more active and less toxic than conventional camptothecins and can induce cancer cell apoptosis. However, the mechanisms of HCPT-induced apoptosis in colon cancer cells remain unclear. In this study, we investigated the effects of HCPT on apoptosis of colon cancer and underlying mechanism.

Methods

Cell proliferation was measured by MTT (3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide) assay, and apoptosis was measured using terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick end labeling (TUNEL) assay. Expression of genes was detected using real-time reverse transcription-polymerase chain reaction (real time-PCR) and Western blot. Tumor growth in vivo was evaluated using a nude mouse xenograft model.

Results

HCPT could significantly inhibit cell proliferation and induce apoptosis in colon cancer SW1116 and Colo 205 cells in dose- and time-dependent manners. HCPT treatment activated the activities of caspase 3, 7, 8 and 9, downregulated the expression of survivin, survivinΔEx3, survivin-3B and XIAP, and upregulated expression of surviving 2B. Moreover, the combination of HCPT and 5-fluorouracial (5-FU) synergistically induced apoptosis and downregulated the expression of survivin and XIAP. Knockdown of survivin and XIAP by siRNA sensitized colon cancer to HCTP-induced apoptosis. Furthermore, HCPT treatment significantly inhibited SW1116 xenograft tumor growth.

Conclusions

Our results elucidate new mechanisms of HCPT antitumor by the downregulation of survivin and XIAP expression. The combination of HCPT with 5-FU or IAP inhibitors may be a potential strategy for colon cancer treatment.

【 授权许可】

   
2013 Fei et al.; licensee BioMed Central Ltd.

【 图 表 】

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