Abstract:
:Autophagy is a complex of adaptive cellular response that enhances cancer cell survival in the face of cellular stresses such as chemotherapy. Recently, chloroquine diphosphate (CQ), a widely used antimalarial drug, has been studied as a potential inhibitor of autophagy. Here, we aimed to investigate the role of CQ in potentiating the effect of 5-fluorouracil (5-FU), the chemotherapeutic agent of first choice for the treatment of colorectal cancer, in an animal model of colon cancer. The mouse colon cancer cell line colon26 was used. For the in-vivo study, colon26 cells were injected subcutaneously into BALB/c mice, which were treated with saline as a control, CQ (50 mg/kg/day), 5-FU (30 mg/kg/day), or the combination therapy (CQ plus 5-FU). The tumor volume ratio and body weight were monitored. After the sacrifice, tumor tissue protein extracts and tumor sections were prepared and subjected to immunoblotting for the analysis of autophagy-related and apoptosis-related proteins, and the terminal transferase uridyl end labeling assay. The combination of CQ resulted in the inhibition of 5-FU-induced autophagy and a significant enhancement in the 5-FU-induced inhibition of tumor growth. Furthermore, the combination treatment of CQ and 5-FU resulted in a significant increase in the ratio of apoptotic cells compared with other treatments. The expression levels of the proapoptotic proteins, namely Bad and Bax, were increased by the CQ treatment in the protein extracts from tumors. Our findings suggest that the combination therapy of CQ and 5-FU should be considered as an effective strategy for the treatment of colorectal cancer.
journal_name
Anticancer Drugsjournal_title
Anti-cancer drugsauthors
Sasaki K,Tsuno NH,Sunami E,Kawai K,Hongo K,Hiyoshi M,Kaneko M,Murono K,Tada N,Nirei T,Takahashi K,Kitayama Jdoi
10.1097/CAD.0b013e328353f8c7subject
Has Abstractpub_date
2012-08-01 00:00:00pages
675-82issue
7eissn
0959-4973issn
1473-5741journal_volume
23pub_type
杂志文章abstract::Renal cell carcinoma (RCC) is one of the most frequent malignancies of the adults. Its incidence has been increasing steadily by 2-4% each year. Up to 30% of patients present with metastases at diagnosis. It is a highly vascularized cancer because of the hypoxia-induced factor stabilization as a consequence of von Hip...
journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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journal_title:Anti-cancer drugs
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doi:10.1097/CAD.0b013e32835a0fbd
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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doi:10.1097/CAD.0b013e32833d5ec0
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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doi:10.1097/CAD.0b013e3283635a47
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
doi:10.1097/00001813-199010000-00011
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章,评审
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
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journal_title:Anti-cancer drugs
pub_type: 杂志文章
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abstract::The current reference treatment of hormone-refractory prostate cancer consists mainly of chemotherapy with docetaxel. To improve the management of advanced prostate cancer, one should examine the benefits of adding other agents to docetaxel. We examined the growth inhibitory effects of a triple combination, including ...
journal_title:Anti-cancer drugs
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abstract::Silibinin, with a strong antioxidant activity and a weak cytotoxic property, is considered a candidate for cancer prevention. As there is no information on its effect on breast cancer tumor-initiating cells [cancer stem cells (CSCs)] in a 3D culture model, which more closely mimic natural tissues, we carried out this ...
journal_title:Anti-cancer drugs
pub_type: 杂志文章
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更新日期:2015-06-01 00:00:00
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journal_title:Anti-cancer drugs
pub_type: 临床试验,杂志文章,多中心研究
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